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Sample records for chromosome segregation

  1. Mechanisms for chromosome segregation.

    Science.gov (United States)

    Bouet, Jean-Yves; Stouf, Mathieu; Lebailly, Elise; Cornet, François

    2014-12-01

    Bacteria face the problem of segregating their gigantic chromosomes without a segregation period restricted in time and space, as Eukaryotes do. Segregation thus involves multiple activities, general or specific of a chromosome region and differentially controlled. Recent advances show that these various mechanisms conform to a “pair and release” rule, which appears as a general rule in DNA segregation. We describe the latest advances in segregation of bacterial chromosomes with emphasis on the different pair and release mechanisms.

  2. Bacterial chromosome segregation.

    Science.gov (United States)

    Possoz, Christophe; Junier, Ivan; Espeli, Olivier

    2012-01-01

    Dividing cells have mechanisms to ensure that their genomes are faithfully segregated into daughter cells. In bacteria, the description of these mechanisms has been considerably improved in the recent years. This review focuses on the different aspects of bacterial chromosome segregation that can be understood thanks to the studies performed with model organisms: Escherichia coli, Bacillus subtilis, Caulobacter crescentus and Vibrio cholerae. We describe the global positionning of the nucleoid in the cell and the specific localization and dynamics of different chromosomal loci, kinetic and biophysic aspects of chromosome segregation are presented. Finally, a presentation of the key proteins involved in the chromosome segregation is made.

  3. Chromosome segregation in Vibrio cholerae.

    Science.gov (United States)

    Ramachandran, Revathy; Jha, Jyoti; Chattoraj, Dhruba K

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae compare with those in other bacteria, and highlight some of the remaining questions regarding the process of bacterial chromosome segregation.

  4. Chromosome Segregation in Vibrio cholerae

    OpenAIRE

    Ramachandran, R.; Jha, J.; Chattoraj, DK

    2014-01-01

    The study of chromosome segregation is currently one of the most exciting research frontiers in cell biology. In this review, we discuss our current knowledge of the chromosome segregation process in Vibrio cholerae, based primarily on findings from fluorescence microscopy experiments. This bacterium is of special interest because of its eukaryotic feature of having a divided genome, a feature shared with 10% of known bacteria. We also discuss how the segregation mechanisms of V. cholerae com...

  5. Chromosome segregation in plant meiosis

    Directory of Open Access Journals (Sweden)

    Linda eZamariola

    2014-06-01

    Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.

  6. Bacterial chromosome organization and segregation.

    Science.gov (United States)

    Badrinarayanan, Anjana; Le, Tung B K; Laub, Michael T

    2015-01-01

    If fully stretched out, a typical bacterial chromosome would be nearly 1 mm long, approximately 1,000 times the length of a cell. Not only must cells massively compact their genetic material, but they must also organize their DNA in a manner that is compatible with a range of cellular processes, including DNA replication, DNA repair, homologous recombination, and horizontal gene transfer. Recent work, driven in part by technological advances, has begun to reveal the general principles of chromosome organization in bacteria. Here, drawing on studies of many different organisms, we review the emerging picture of how bacterial chromosomes are structured at multiple length scales, highlighting the functions of various DNA-binding proteins and the impact of physical forces. Additionally, we discuss the spatial dynamics of chromosomes, particularly during their segregation to daughter cells. Although there has been tremendous progress, we also highlight gaps that remain in understanding chromosome organization and segregation.

  7. Bacterial Chromosome Organization and Segregation

    OpenAIRE

    Toro, Esteban; Shapiro, Lucy

    2010-01-01

    Bacterial chromosomes are generally ∼1000 times longer than the cells in which they reside, and concurrent replication, segregation, and transcription/translation of this crowded mass of DNA poses a challenging organizational problem. Recent advances in cell-imaging technology with subdiffraction resolution have revealed that the bacterial nucleoid is reliably oriented and highly organized within the cell. Such organization is transmitted from one generation to the next by progressive segrega...

  8. Entropy as the driver of chromosome segregation.

    Science.gov (United States)

    Jun, Suckjoon; Wright, Andrew

    2010-08-01

    We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.

  9. Chromosome replication and segregation in bacteria.

    Science.gov (United States)

    Reyes-Lamothe, Rodrigo; Nicolas, Emilien; Sherratt, David J

    2012-01-01

    In dividing cells, chromosome duplication once per generation must be coordinated with faithful segregation of newly replicated chromosomes and with cell growth and division. Many of the mechanistic details of bacterial replication elongation are well established. However, an understanding of the complexities of how replication initiation is controlled and coordinated with other cellular processes is emerging only slowly. In contrast to eukaryotes, in which replication and segregation are separate in time, the segregation of most newly replicated bacterial genetic loci occurs sequentially soon after replication. We compare the strategies used by chromosomes and plasmids to ensure their accurate duplication and segregation and discuss how these processes are coordinated spatially and temporally with growth and cell division. We also describe what is known about the three conserved families of ATP-binding proteins that contribute to chromosome segregation and discuss their inter-relationships in a range of disparate bacteria.

  10. Entropy as the driver of chromosome segregation

    OpenAIRE

    Jun, Suckjoon; Wright, Andrew

    2010-01-01

    We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in...

  11. Progressive segregation of the Escherichia coli chromosome

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2006-01-01

    We have followed the fate of 14 different loci around the Escherichia coli chromosome in living cells at slow growth rate using a highly efficient labelling system and automated measurements. Loci are segregated as they are replicated, but with a marked delay. Most markers segregate in a smooth...

  12. Dynamics of chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck

    2007-01-01

    Since the 1960’es the conformation and segregation of the chromosome in Escherichia coli has been a subject of interest for many scientists. However, after 40 years of research, we still know incredibly little about how the chromosome is organized inside the cell, how it manages to duplicate...

  13. Chromosome Segregation: Organizing Overlap at the Midzone

    NARCIS (Netherlands)

    Janson, M.E.; Tran, P.T.

    2008-01-01

    Sets of overlapping microtubules support the segregation of chromosomes by linking the poles of mitotic spindles. Recent work examines the effect of putting these linkages under pressure by the activation of dicentric chromosomes and sheds new light on the structural role of several well-known spind

  14. PICH promotes mitotic chromosome segregation

    DEFF Research Database (Denmark)

    Nielsen, Christian Thomas Friberg; Hickson, Ian D

    2016-01-01

    PICH is an SNF2-family DNA translocase that appears to play a role specifically in mitosis. Characterization of PICH in human cells led to the initial discovery of "ultra-fine DNA bridges" (UFBs) that connect the 2 segregating DNA masses in the anaphase of mitosis. These bridge structures, which...

  15. Controlling segregation speed of entangled polymers by the shapes: A simple model for eukaryotic chromosome segregation

    Science.gov (United States)

    Sakai, Yuji; Tachikawa, Masashi; Mochizuki, Atsushi

    2016-10-01

    We report molecular dynamics simulations of the segregation of two overlapping polymers motivated by chromosome segregation in biological cells. We investigate the relationship between polymer shapes and segregation dynamics and show that elongation and compaction make entangled polymers segregate rapidly. This result suggests that eukaryotic chromosomes take such a characteristic rod-shaped structure, which is induced by condensins, to achieve rapid segregation.

  16. Plasmid and chromosome segregation in prokaryotes

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Bugge Jensen, Rasmus; Gerdes, Kenn

    2000-01-01

    Recent major advances in the understanding of prokaryotic DNA segregation have been achieved by using fluorescence microscopy to visualize the localization of cellular components. Plasmids and bacterial chromosomes are partitioned in a highly dynamic fashion, suggesting the presence of a mitotic......-like apparatus in prokaryotes. The identification of chromosomal homologues of the well-characterized plasmid partitioning genes indicates that there could be a general mechanism of bacterial DNA partitioning. Udgivelsesdato: July 1...

  17. Organization and segregation of bacterial chromosomes.

    Science.gov (United States)

    Wang, Xindan; Montero Llopis, Paula; Rudner, David Z

    2013-03-01

    The bacterial chromosome must be compacted more than 1,000-fold to fit into the compartment in which it resides. How it is condensed, organized and ultimately segregated has been a puzzle for over half a century. Recent advances in live-cell imaging and genome-scale analyses have led to new insights into these problems. We argue that the key feature of compaction is the orderly folding of DNA along adjacent segments and that this organization provides easy and efficient access for protein-DNA transactions and has a central role in driving segregation. Similar principles and common proteins are used in eukaryotes to condense and to resolve sister chromatids at metaphase.

  18. SMC complexes in bacterial chromosome condensation and segregation.

    Science.gov (United States)

    Strunnikov, Alexander V

    2006-03-01

    Bacterial chromosomes segregate via a partition apparatus that employs a score of specialized proteins. The SMC complexes play a crucial role in the chromosome partitioning process by organizing bacterial chromosomes through their ATP-dependent chromatin-compacting activity. Recent progress in the composition of these complexes and elucidation of their structural and enzymatic properties has advanced our comprehension of chromosome condensation and segregation mechanics in bacteria.

  19. SMC complexes in bacterial chromosome condensation and segregation

    OpenAIRE

    Strunnikov, Alexander V.

    2005-01-01

    Bacterial chromosomes segregate via a partition apparatus that employs a score of specialized proteins. The SMC complexes play a crucial role in the chromosome partitioning process by organizing bacterial chromosomes through their ATP-dependent chromatin-compacting activity. Recent progress in the composition of these complexes and elucidation of their structural and enzymatic properties has advanced our comprehension of chromosome condensation and segregation mechanics in bacteria.

  20. Dynamics of Escherichia coli chromosome segregation during multifork replication.

    Science.gov (United States)

    Nielsen, Henrik J; Youngren, Brenda; Hansen, Flemming G; Austin, Stuart

    2007-12-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks.

  1. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication▿

    Science.gov (United States)

    Nielsen, Henrik J.; Youngren, Brenda; Hansen, Flemming G.; Austin, Stuart

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks. PMID:17905986

  2. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  3. Growth conditions regulate the requirements for Caulobacter chromosome segregation.

    Science.gov (United States)

    Shebelut, Conrad W; Jensen, Rasmus B; Gitai, Zemer

    2009-02-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated.

  4. Caulobacter chromosome segregation is an ordered multistep process.

    Science.gov (United States)

    Shebelut, Conrad W; Guberman, Jonathan M; van Teeffelen, Sven; Yakhnina, Anastasiya A; Gitai, Zemer

    2010-08-10

    Despite its fundamental nature, bacterial chromosome segregation remains poorly understood. Viewing segregation as a single process caused multiple proposed mechanisms to appear in conflict and failed to explain how asymmetrically dividing bacteria break symmetry to move only one of their chromosomes. Here, we demonstrate that the ParA ATPase extends from one cell pole and pulls the chromosome by retracting upon association with the ParB DNA-binding protein. Surprisingly, ParA disruption has a specific effect on chromosome segregation that only perturbs the latter stages of this process. Using quantitative high-resolution imaging, we demonstrate that this specificity results from the multistep nature of chromosome translocation. We propose that Caulobacter chromosome segregation follows an ordered pathway of events with distinct functions and mechanisms. Initiation releases polar tethering of the origin of replication, distinction spatially differentiates the two chromosomes, and commitment irreversibly translocates the distal centromeric locus. Thus, much as eukaryotic mitosis involves a sequence of distinct subprocesses, Caulobacter cells also segregate their chromosomes through an orchestrated series of steps. We discuss how the multistep view of bacterial chromosome segregation can help to explain and reconcile outstanding puzzles and frame future investigation.

  5. CHROMOSOME SEGREGATION: NOVEL INSIGHTS INTO THE MECHANISM AND REGULATION

    Directory of Open Access Journals (Sweden)

    Miroslava Pozgajova

    2013-02-01

    Full Text Available A crucial feature of every healthy living organism is accurate segregation of chromosomes. Errors in this process may lead to aneuploidy, which is responsible for diverse genetic defects and diseases such as Down syndrome, miscarriages, cancer and others. Although, chromosome segregation has been studied intensively in the past, the exact mechanism of accurate chromosome segregation still remains unclear. Identification and characterization of proteins and protein complexes involved in this process is essential for understanding of processes that lead to chromosome missegregation. Basic molecular mechanism share common principles in animals, humans, plants and unicellular organisms; it is therefore possible to study these mechanisms in simple model organisms such as yeasts. The fission yeast Schizosaccharomyces pombe is an excellent model organism to study the function and regulation of chromosome segregation in both mitosis and meiosis.

  6. The Consequences of Chromosome Segregation Errors in Mitosis and Meiosis

    Directory of Open Access Journals (Sweden)

    Tamara Potapova

    2017-02-01

    Full Text Available Mistakes during cell division frequently generate changes in chromosome content, producing aneuploid or polyploid progeny cells. Polyploid cells may then undergo abnormal division to generate aneuploid cells. Chromosome segregation errors may also involve fragments of whole chromosomes. A major consequence of segregation defects is change in the relative dosage of products from genes located on the missegregated chromosomes. Abnormal expression of transcriptional regulators can also impact genes on the properly segregated chromosomes. The consequences of these perturbations in gene expression depend on the specific chromosomes affected and on the interplay of the aneuploid phenotype with the environment. Most often, these novel chromosome distributions are detrimental to the health and survival of the organism. However, in a changed environment, alterations in gene copy number may generate a more highly adapted phenotype. Chromosome segregation errors also have important implications in human health. They may promote drug resistance in pathogenic microorganisms. In cancer cells, they are a source for genetic and phenotypic variability that may select for populations with increased malignance and resistance to therapy. Lastly, chromosome segregation errors during gamete formation in meiosis are a primary cause of human birth defects and infertility. This review describes the consequences of mitotic and meiotic errors focusing on novel concepts and human health.

  7. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division...

  8. Tracking of chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes chromosome segregation.

    Science.gov (United States)

    Kjos, Morten; Veening, Jan-Willem

    2014-03-01

    Chromosome segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval-shaped streptococci. Using time-lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of chromosome segregation in live cells of the human pathogen Streptococcus pneumoniae. Our observations show that the chromosome segregation process last for two-thirds of the total cell cycle; the origin region segregates rapidly in the early stages of the cell cycle while nucleoid segregation finishes just before cell division. Previously we have demonstrated that the DNA-binding protein ParB and the condensin SMC promote efficient chromosome segregation, likely by an active mechanism. We now show that in the absence of SMC, cell division can occur over the unsegregated chromosomes. However, neither smc nor parB are essential in S. pneumoniae, suggesting the importance of additional mechanisms. Here we have identified the process of transcription as one of these mechanisms important for chromosome segregation in S. pneumoniae. Transcription inhibitors rifampicin and streptolydigin as well as mutants affected in transcription elongation cause chromosome segregation defects. Together, our results highlight the importance of passive (or indirect) processes such as transcription for chromosome segregation in oval-shaped bacteria.

  9. A dynamic, mitotic-like mechanism for bacterial chromosome segregation.

    Science.gov (United States)

    Fogel, Michael A; Waldor, Matthew K

    2006-12-01

    The mechanisms that mediate chromosome segregation in bacteria are poorly understood. Despite evidence of dynamic movement of chromosome regions, to date, mitotic-like mechanisms that act on the bacterial chromosome have not been demonstrated. Here we provide evidence that the Vibrio cholerae ParAI and ParBI proteins are components of an apparatus that pulls the origin region of the large V. cholerae chromosome to the cell pole and anchors it there. ParBI interacts with a conserved origin-proximal, centromere-like site (parSI) that, following chromosome replication, segregates asymmetrically from one pole to the other. While segregating, parSI stretches far away from neighboring chromosomal loci. ParAI forms a dynamic band that extends from the pole to the segregating ParBI/parSI complex. Movement of ParBI/parSI across the cell occurs in concert with ParAI retraction. Deletion of parAI disrupts proper origin localization and segregation dynamics, and parSI no longer separates from nearby regions. These data suggest that ParAI forms a dynamic structure that pulls the ParBI-bound chromosome to the pole in a process analogous to anaphase of eukaryotic mitosis.

  10. Tracking of chromosome dynamics in live Streptococcus pneumoniae reveals that transcription promotes chromosome segregation

    NARCIS (Netherlands)

    Kjos, Morten; Veening, Jan-Willem

    2014-01-01

    Chromosome segregation is an essential part of the bacterial cell cycle but is poorly characterized in oval-shaped streptococci. Using time-lapse fluorescence microscopy and total internal reflection fluorescence microscopy, we have tracked the dynamics of chromosome segregation in live cells of the

  11. Escherichia coli Chromosomal Loci Segregate from Midcell with Universal Dynamics.

    Science.gov (United States)

    Cass, Julie A; Kuwada, Nathan J; Traxler, Beth; Wiggins, Paul A

    2016-06-21

    The structure of the Escherichia coli chromosome is inherently dynamic over the duration of the cell cycle. Genetic loci undergo both stochastic motion around their initial positions and directed motion to opposite poles of the rod-shaped cell during segregation. We developed a quantitative method to characterize cell-cycle dynamics of the E. coli chromosome to probe the chromosomal steady-state mobility and segregation process. By tracking fluorescently labeled chromosomal loci in thousands of cells throughout the entire cell cycle, our method allows for the statistical analysis of locus position and motion, the step-size distribution for movement during segregation, and the locus drift velocity. The robust statistics of our detailed analysis of the wild-type E. coli nucleoid allow us to observe loci moving toward midcell before segregation occurs, consistent with a replication factory model. Then, as segregation initiates, we perform a detailed characterization of the average segregation velocity of loci. Contrary to origin-centric models of segregation, which predict distinct dynamics for oriC-proximal versus oriC-distal loci, we find that the dynamics of loci were universal and independent of genetic position.

  12. Chromosome segregation errors: a double-edged sword

    NARCIS (Netherlands)

    Janssen, A.

    2012-01-01

    Unequal separation of the mother cells’ DNA over its two daughter cells upon cell division is a prevalent phenotype found in cancer cells. This imbalanced nuclear division manifests itself as chromosome segregation errors in the final phases of Mitosis. Chromosome unstable (CIN) cancer cells continu

  13. Diversity and redundancy in bacterial chromosome segregation mechanisms.

    Science.gov (United States)

    Errington, Jeff; Murray, Heath; Wu, Ling Juan

    2005-03-29

    Bacterial cells are much smaller and have a much simpler overall structure and organization than eukaryotes. Several prominent differences in cell organization are relevant to the mechanisms of chromosome segregation, particularly the lack of an overt chromosome condensation/decondensation cycle and the lack of a microtubule-based spindle. Although bacterial chromosomes have a rather dispersed appearance, they nevertheless have an underlying high level of spatial organization. During the DNA replication cycle, early replicated (oriC) regions are localized towards the cell poles, whereas the late replicated terminus (terC) region is medially located. This spatial organization is thought to be driven by an active segregation mechanism that separates the sister chromosomes continuously as replication proceeds. Comparisons of various well-characterized bacteria suggest that the mechanisms of chromosome segregation are likely to be diverse, and that in many bacteria, multiple overlapping mechanisms may contribute to efficient segregation. One system in which the molecular mechanisms of chromosome segregation are beginning to be elucidated is that of sporulating cells of Bacillus subtilis. The key components of this system have been identified, and their functions are understood, in outline. Although this system appears to be specialized, most of the functions are conserved widely throughout the bacteria.

  14. The spindle checkpoint and chromosome segregation in meiosis.

    Science.gov (United States)

    Gorbsky, Gary J

    2015-07-01

    The spindle checkpoint is a key regulator of chromosome segregation in mitosis and meiosis. Its function is to prevent precocious anaphase onset before chromosomes have achieved bipolar attachment to the spindle. The spindle checkpoint comprises a complex set of signaling pathways that integrate microtubule dynamics, biomechanical forces at the kinetochores, and intricate regulation of protein interactions and post-translational modifications. Historically, many key observations that gave rise to the initial concepts of the spindle checkpoint were made in meiotic systems. In contrast with mitosis, the two distinct chromosome segregation events of meiosis present a special challenge for the regulation of checkpoint signaling. Preservation of fidelity in chromosome segregation in meiosis, controlled by the spindle checkpoint, also has a significant impact in human health. This review highlights the contributions from meiotic systems in understanding the spindle checkpoint as well as the role of checkpoint signaling in controlling the complex divisions of meiosis.

  15. An SMC ATPase mutant disrupts chromosome segregation in Caulobacter.

    Science.gov (United States)

    Schwartz, Monica A; Shapiro, Lucy

    2011-12-01

    Accurate replication and segregation of the bacterial genome are essential for cell cycle progression. We have identified a single amino acid substitution in the Caulobacter structural maintenance of chromosomes (SMC) protein that disrupts chromosome segregation and cell division. The E1076Q point mutation in the SMC ATPase domain caused a dominant-negative phenotype in which DNA replication was able to proceed, but duplicated parS centromeres, normally found at opposite cell poles, remained at one pole. The cellular positions of other chromosomal loci were in the wild-type order relative to the parS centromere, but chromosomes remained unsegregated and appeared to be stacked upon one another. Purified SMC-E1076Q was deficient in ATP hydrolysis and exhibited abnormally stable binding to DNA. We propose that SMC spuriously links the duplicated chromosome immediately after passage of the replication fork. In wild-type cells, ATP hydrolysis opens the SMC dimer, freeing one chromosome to segregate to the opposite pole. The loss of ATP hydrolysis causes the SMC-E1076Q dimer to remain bound to both chromosomes, inhibiting segregation.

  16. Abnormal Chromosome Segregation May Trigger Tumors

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Cancer is a primary threat to human health as it kills millions of people each year.Scientists have shown that 75% of human cancers have an abnormal number of chromosomes in cells,and the proportion of the cells with an abnormal chromosome number is tightly and positively related to malignance progression and metastasis of cancers. But the pathological mechanism behind the anomaly still remains unknown.

  17. RNAi pathway participates in chromosome segregation in mammalian cells.

    Science.gov (United States)

    Huang, Chuan; Wang, Xiaolin; Liu, Xu; Cao, Shuhuan; Shan, Ge

    2015-01-01

    The RNAi machinery is a mighty regulator in a myriad of life events. Despite lines of evidence that small RNAs and components of the RNAi pathway may be associated with structure and behavior of mitotic chromosomes in diverse organisms, a direct role of the RNAi pathway in mammalian mitotic chromosome segregation remains elusive. Here we report that Dicer and AGO2, two central components of the mammalian RNAi pathway, participate in the chromosome segregation. Knockdown of Dicer or AGO2 results in a higher incidence of chromosome lagging, and this effect is independent from microRNAs as examined with DGCR8 knockout cells. Further investigation has revealed that α-satellite RNA, a noncoding RNA derived from centromeric repeat region, is managed by AGO2 under the guidance of endogenous small interference RNAs (ASAT siRNAs) generated by Dicer. Furthermore, the slicer activity of AGO2 is essential for the chromosome segregation. Level and distribution of chromosome-associated α-satellite RNA have crucial regulatory effect on the localization of centromeric proteins such as centromere protein C1 (CENPC1). With these results, we also provide a paradigm in which the RNAi pathway participates in vital cellular events through the maintenance of level and distribution of noncoding RNAs in cells.

  18. Systematic analysis of human protein complexes identifies chromosome segregation proteins.

    Science.gov (United States)

    Hutchins, James R A; Toyoda, Yusuke; Hegemann, Björn; Poser, Ina; Hériché, Jean-Karim; Sykora, Martina M; Augsburg, Martina; Hudecz, Otto; Buschhorn, Bettina A; Bulkescher, Jutta; Conrad, Christian; Comartin, David; Schleiffer, Alexander; Sarov, Mihail; Pozniakovsky, Andrei; Slabicki, Mikolaj Michal; Schloissnig, Siegfried; Steinmacher, Ines; Leuschner, Marit; Ssykor, Andrea; Lawo, Steffen; Pelletier, Laurence; Stark, Holger; Nasmyth, Kim; Ellenberg, Jan; Durbin, Richard; Buchholz, Frank; Mechtler, Karl; Hyman, Anthony A; Peters, Jan-Michael

    2010-04-30

    Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate that the identity and composition of these protein complexes is incompletely understood. Using gene tagging on bacterial artificial chromosomes, protein localization, and tandem-affinity purification-mass spectrometry, the MitoCheck consortium has analyzed about 100 human protein complexes, many of which had not or had only incompletely been characterized. This work has led to the discovery of previously unknown, evolutionarily conserved subunits of the anaphase-promoting complex and the gamma-tubulin ring complex--large complexes that are essential for spindle assembly and chromosome segregation. The approaches we describe here are generally applicable to high-throughput follow-up analyses of phenotypic screens in mammalian cells.

  19. A spindle-like apparatus guides bacterial chromosome segregation.

    Science.gov (United States)

    Ptacin, Jerod L; Lee, Steven F; Garner, Ethan C; Toro, Esteban; Eckart, Michael; Comolli, Luis R; Moerner, W E; Shapiro, Lucy

    2010-08-01

    Until recently, a dedicated mitotic apparatus that segregates newly replicated chromosomes into daughter cells was believed to be unique to eukaryotic cells. Here we demonstrate that the bacterium Caulobacter crescentus segregates its chromosome using a partitioning (Par) apparatus that has surprising similarities to eukaryotic spindles. We show that the C. crescentus ATPase ParA forms linear polymers in vitro and assembles into a narrow linear structure in vivo. The centromere-binding protein ParB binds to and destabilizes ParA structures in vitro. We propose that this ParB-stimulated ParA depolymerization activity moves the centromere to the opposite cell pole through a burnt bridge Brownian ratchet mechanism. Finally, we identify the pole-specific TipN protein as a new component of the Par system that is required to maintain the directionality of DNA transfer towards the new cell pole. Our results elucidate a bacterial chromosome segregation mechanism that features basic operating principles similar to eukaryotic mitotic machines, including a multivalent protein complex at the centromere that stimulates the dynamic disassembly of polymers to move chromosomes into daughter compartments.

  20. Time scale of entropic segregation of flexible polymers in confinement: Implications for chromosome segregation in filamentous bacteria

    OpenAIRE

    Arnold, Axel; Jun, Suckjoon

    2007-01-01

    We report molecular dynamics simulations of the segregation of two overlapping chains in cylindrical confinement. We find that the entropic repulsion between the chains can be sufficiently strong to cause segregation on a time scale that is short compared to the one for diffusion. This result implies that entropic driving forces are sufficiently strong to cause rapid bacterial chromosome segregation.

  1. Time scale of entropic segregation of flexible polymers in confinement: Implications for chromosome segregation in filamentous bacteria

    Science.gov (United States)

    Arnold, Axel; Jun, Suckjoon

    2007-09-01

    We report molecular dynamics simulations of the segregation of two overlapping chains in cylindrical confinement. We find that the entropic repulsion between chains can be sufficiently strong to cause segregation on a time scale that is short compared to the one for diffusion. This result implies that entropic driving forces are sufficiently strong to cause rapid bacterial chromosome segregation.

  2. Acentrosomal spindle assembly and chromosome segregation during oocyte meiosis.

    Science.gov (United States)

    Dumont, Julien; Desai, Arshad

    2012-05-01

    The ability to reproduce relies in most eukaryotes on specialized cells called gametes. Gametes are formed by the process of meiosis in which, after a single round of replication, two successive cell divisions reduce the ploidy of the genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal species, chromosome segregation during female meiosis occurs on spindles assembled in the absence of the major microtubule-organizing center, the centrosome. In mammals, oocyte meiosis is error prone and underlies most birth aneuploidies. Here, we review recent work on acentrosomal spindle formation and chromosome alignment/separation during oocyte meiosis in different animal models.

  3. Acentrosomal Spindle Assembly & Chromosome Segregation During Oocyte Meiosis

    OpenAIRE

    Dumont, Julien; Desai, Arshad

    2012-01-01

    The ability to reproduce relies in most eukaryotes on specialized cells called gametes. Gametes are formed by the process of meiosis in which, after a single round of replication, two successive cell divisions reduce the ploidy of the genome. Fusion of gametes at fertilization reconstitutes diploidy. In most animal species, chromosome segregation during female meiosis occurs on spindles assembled in the absence of the major microtubule-organizing center, the centrosome. In mammals, oocyte mei...

  4. Proposed Physical Mechanism of Chromosome Segregation in Caulobacter crescentus

    Science.gov (United States)

    Banigan, Edward; Gelbart, Michael; Gitai, Zemer; Liu, Andrea; Wingreen, Ned

    2010-03-01

    Chromosome segregation is a fundamental process for all cells, but the force-generating mechanisms that drive chromosome movements in bacteria are especially unclear. In Caulobacter crescentus, recent work has demonstrated that a structure made up of the ParA protein elongates from one cell pole and interacts with ParB, a protein binding to the chromosome near the origin of replication (ori). ParB disassembles ParA, causing ParA to pull ParB, and thus, the ori to the opposite end of the cell. We performed Brownian dynamics simulations of this system in order to uncover the physical mechanism of this motion. We find that motion of the ori is robust to several variations of the model as long as a steady-state concentration gradient of ParA is established in the moving frame of the ParB-decorated chromosome. We suggest that the mechanism is ``self-diffusiophoretic'': by disassembling ParA, ParB creates a concentration gradient of ParA so that the ParA concentration is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the gradient in the desired direction.

  5. Back to the roots: segregation of univalent sex chromosomes in meiosis.

    Science.gov (United States)

    Fabig, Gunar; Müller-Reichert, Thomas; Paliulis, Leocadia V

    2016-06-01

    In males of many taxa, univalent sex chromosomes normally segregate during the first meiotic division, and analysis of sex chromosome segregation was foundational for the chromosome theory of inheritance. Correct segregation of single or multiple univalent sex chromosomes occurs in a cellular environment where every other chromosome is a bivalent that is being partitioned into homologous chromosomes at anaphase I. The mechanics of univalent chromosome segregation vary among animal taxa. In some, univalents establish syntelic attachment of sister kinetochores to the spindle. In others, amphitelic attachment is established. Here, we review how this problem of segregation of unpaired chromosomes is solved in different animal systems. In addition, we give a short outlook of how mechanistic insights into this process could be gained by explicitly studying model organisms, such as Caenorhabditis elegans.

  6. Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation

    OpenAIRE

    Measday, Vivien; Baetz, Kristin; Guzzo, Julie; Yuen, Karen; Kwok, Teresa; Sheikh, Bilal; Ding, Huiming; Ueta, Ryo; Hoac, Trinh; Cheng, Benjamin; Pot, Isabelle; Tong, Amy; Yamaguchi-Iwai, Yuko; Boone, Charles; Hieter, Phil

    2005-01-01

    Accurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosom...

  7. Chromosome segregation proteins of Vibrio cholerae as transcription regulators.

    Science.gov (United States)

    Baek, Jong Hwan; Rajagopala, Seesandra V; Chattoraj, Dhruba K

    2014-05-06

    ABSTRACT Bacterial ParA and ParB proteins are best known for their contribution to plasmid and chromosome segregation, but they may also contribute to other cell functions. In segregation, ParA interacts with ParB, which binds to parS centromere-analogous sites. In transcription, plasmid Par proteins can serve as repressors by specifically binding to their own promoters and, additionally, in the case of ParB, by spreading from a parS site to nearby promoters. Here, we have asked whether chromosomal Par proteins can likewise control transcription. Analysis of genome-wide ParB1 binding in Vibrio cholerae revealed preferential binding to the three known parS1 sites and limited spreading of ParB1 beyond the parS1 sites. Comparison of wild-type transcriptomes with those of ΔparA1, ΔparB1, and ΔparAB1 mutants revealed that two out of 20 genes (VC0067 and VC0069) covered by ParB1 spreading are repressed by both ParB1 and ParA1. A third gene (VC0076) at the outskirts of the spreading area and a few genes further away were also repressed, particularly the gene for an outer membrane protein, ompU (VC0633). Since ParA1 or ParB1 binding was not evident near VC0076 and ompU genes, the repression may require participation of additional factors. Indeed, both ParA1 and ParB1 proteins were found to interact with several V. cholerae proteins in bacterial and yeast two-hybrid screens. These studies demonstrate that chromosomal Par proteins can repress genes unlinked to parS and can do so without direct binding to the cognate promoter DNA. IMPORTANCE Directed segregation of chromosomes is essential for their maintenance in dividing cells. Many bacteria have genes (par) that were thought to be dedicated to segregation based on analogy to their roles in plasmid maintenance. It is becoming clear that chromosomal par genes are pleiotropic and that they contribute to diverse processes such as DNA replication, cell division, cell growth, and motility. One way to explain the pleiotropy

  8. Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes.

    Science.gov (United States)

    Holubcová, Zuzana; Blayney, Martyn; Elder, Kay; Schuh, Melina

    2015-06-05

    Aneuploidy in human eggs is the leading cause of pregnancy loss and several genetic disorders such as Down syndrome. Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg's progenitor cell. The basis for particularly error-prone chromosome segregation in human oocytes is not known. We analyzed meiosis in more than 100 live human oocytes and identified an error-prone chromosome-mediated spindle assembly mechanism as a major contributor to chromosome segregation defects. Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours. This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.

  9. MreB actin-mediated segregation of a specific region of a bacterial chromosome.

    Science.gov (United States)

    Gitai, Zemer; Dye, Natalie Anne; Reisenauer, Ann; Wachi, Masaaki; Shapiro, Lucy

    2005-02-11

    Faithful chromosome segregation is an essential component of cell division in all organisms. The eukaryotic mitotic machinery uses the cytoskeleton to move specific chromosomal regions. To investigate the potential role of the actin-like MreB protein in bacterial chromosome segregation, we first demonstrate that MreB is the direct target of the small molecule A22. We then demonstrate that A22 completely blocks the movement of newly replicated loci near the origin of replication but has no qualitative or quantitative effect on the segregation of other loci if added after origin segregation. MreB selectively interacts, directly or indirectly, with origin-proximal regions of the chromosome, arguing that the origin-proximal region segregates via an MreB-dependent mechanism not used by the rest of the chromosome.

  10. Replication initiator DnaA binds at the Caulobacter centromere and enables chromosome segregation.

    Science.gov (United States)

    Mera, Paola E; Kalogeraki, Virginia S; Shapiro, Lucy

    2014-11-11

    During cell division, multiple processes are highly coordinated to faithfully generate genetically equivalent daughter cells. In bacteria, the mechanisms that underlie the coordination of chromosome replication and segregation are poorly understood. Here, we report that the conserved replication initiator, DnaA, can mediate chromosome segregation independent of replication initiation. It does so by binding directly to the parS centromere region of the chromosome, and mutations that alter this interaction result in cells that display aberrant centromere translocation and cell division. We propose that DnaA serves to coordinate bacterial DNA replication with the onset of chromosome segregation.

  11. Physical Model of Segregation of E.coli Chromosomes using Molecular Dynamics

    Science.gov (United States)

    Alnahhas, Faisal; Kharel, Savan

    2016-03-01

    Chromosome segregation is one of the most interesting physical processes during a bacterial cell cycle. We will use molecular dynamics simulations which will help us understand how strongly confined polymer segregates. In the presentation, we will discuss how segregation of initially overlapping circular chromosome occurs during a cell cycle. In particular, we will describe the role played by entropic mechanism in the demixing of overlapping circular polymer confined in a cylindrical boundary. We discuss how our polymer chains modeled as an E-coli chromosome experiences an effective repulsion, which ultimately leads to partition driven by the entropic forces. Also, we will also discuss how the segregation of circular chromosome in cylindrical confinement differs from a spherical confinement. Finally, we will discuss the role played by proteins and supercoiling in during the segregation process.

  12. Dysfunctional MreB inhibits chromosome segregation in Escherichia coli

    DEFF Research Database (Denmark)

    Kruse, Thomas; Møller-Jensen, Jakob; Løbner-Olesen, Anders;

    2003-01-01

    The mechanism of prokaryotic chromosome segregation is not known. MreB, an actin homolog, is a shape-determining factor in rod-shaped prokaryotic cells. Using immunofluorescence microscopy we found that MreB of Escherichia coli formed helical filaments located beneath the cell surface. Flow...... cytometric and cytological analyses indicated that MreB-depleted cells segregated their chromosomes in pairs, consistent with chromosome cohesion. Overexpression of wild-type MreB inhibited cell division but did not perturb chromosome segregation. Overexpression of mutant forms of MreB inhibited cell...... division, caused abnormal MreB filament morphology and induced severe localization defects of the nucleoid and of the oriC and terC chromosomal regions. The chromosomal terminus regions appeared cohered in both MreB-depleted cells and in cells overexpressing mutant forms of MreB. Our observations indicate...

  13. Molecular cloaking of H2A.Z on mortal DNA chromosomes during nonrandom segregation.

    Science.gov (United States)

    Huh, Yang Hoon; Sherley, James L

    2011-10-01

    Although nonrandom sister chromatid segregation is a singular property of distributed stem cells (DSCs) that are responsible for renewing and repairing mature vertebrate tissues, both its cellular function and its molecular mechanism remain unknown. This situation persists in part because of the lack of facile methods for detecting and quantifying nonrandom segregating cells and for identifying chromosomes with immortal DNA strands, the cellular molecules that signify nonrandom segregation. During nonrandom segregation, at each mitosis, asymmetrically self-renewing DSCs continuously cosegregate to themselves the set of chromosomes that contain immortal DNA strands, which are the oldest DNA strands. Here, we report the discovery of a molecular asymmetry between segregating sets of immortal chromosomes and opposed mortal chromosomes (i.e., containing the younger set of DNA template strands) that constitutes a new convenient biomarker for detection of cells undergoing nonrandom segregation and direct delineation of chromosomes that bear immortal DNA strands. In both cells engineered with DSC-specific properties and ex vivo-expanded mouse hair follicle stem cells, the histone H2A variant H2A.Z shows specific immunodetection on immortal DNA chromosomes. Cell fixation analyses indicate that H2A.Z is present on mortal chromosomes as well but is cloaked from immunodetection, and the cloaking entity is acid labile. The H2A.Z chromosomal asymmetry produced by molecular cloaking provides a first direct assay for nonrandom segregation and for chromosomes with immortal DNA strands. It also seems likely to manifest an important aspect of the underlying mechanism(s) responsible for nonrandom sister chromatid segregation in DSCs.

  14. Complex polar machinery required for proper chromosome segregation in vegetative and sporulating cells of Bacillus subtilis

    NARCIS (Netherlands)

    Kloosterman, T.G.; Lenarcic, R.; Willis, C.R.; Roberts, D.M.; Hamoen, L.W.; Errington, J.; Wu, L.J.

    2016-01-01

    Chromosome segregation is an essential process of cell multiplication. In prokaryotes, segregation starts with the newly replicated sister origins of replication, oriCs, which move apart to defined positions in the cell. We have developed a genetic screen to identify mutants defective in placement o

  15. Antagonistic spindle motors and MAPs regulate metaphase spindle length and chromosome segregation.

    Science.gov (United States)

    Syrovatkina, Viktoriya; Fu, Chuanhai; Tran, Phong T

    2013-12-02

    Metaphase describes a phase of mitosis where chromosomes are attached and oriented on the bipolar spindle for subsequent segregation at anaphase. In diverse cell types, the metaphase spindle is maintained at characteristic constant length [1-3]. Metaphase spindle length is proposed to be regulated by a balance of pushing and pulling forces generated by distinct sets of spindle microtubules (MTs) and their interactions with motors and MT-associated proteins (MAPs). Spindle length is further proposed to be important for chromosome segregation fidelity, as cells with shorter- or longer-than-normal metaphase spindles, generated through deletion or inhibition of individual mitotic motors or MAPs, showed chromosome segregation defects. To test the force-balance model of spindle length control and its effect on chromosome segregation, we applied fast microfluidic temperature control with live-cell imaging to monitor the effect of deleting or switching off different combinations of antagonistic force contributors in the fission yeast metaphase spindle. We show that the spindle midzone proteins kinesin-5 cut7p and MT bundler ase1p contribute to outward-pushing forces and that the spindle kinetochore proteins kinesin-8 klp5/6p and dam1p contribute to inward-pulling forces. Removing these proteins individually led to aberrant metaphase spindle length and chromosome segregation defects. Removing these proteins in antagonistic combination rescued the defective spindle length and in some combinations also partially rescued chromosome segregation defects.

  16. A minimal number of MELT repeats supports all functions of KNL1 in chromosome segregation

    DEFF Research Database (Denmark)

    Zhang, Gang; Lischetti, Tiziana; Nilsson, Jakob

    2013-01-01

    The Bub1-Bub3 and BubR1-Bub3 checkpoint complexes, or the Bubs, contribute to the accurate segregation of chromosomes during mitosis by promoting chromosome bi-orientation and halting exit from mitosis if this fails. The complexes associate with kinetochores during mitosis, which is required...

  17. Segregation of the replication terminus of the two Vibrio cholerae chromosomes.

    Science.gov (United States)

    Srivastava, Preeti; Fekete, Richard A; Chattoraj, Dhruba K

    2006-02-01

    Genome duplication and segregation normally are completed before cell division in all organisms. The temporal relation of duplication and segregation, however, can vary in bacteria. Chromosomal regions can segregate towards opposite poles as they are replicated or can stay cohered for a considerable period before segregation. The bacterium Vibrio cholerae has two differently sized circular chromosomes, chromosome I (chrI) and chrII, of about 3 and 1 Mbp, respectively. The two chromosomes initiate replication synchronously, and the shorter chrII is expected to complete replication earlier than the longer chrI. A question arises as to whether the segregation of chrII also is completed before that of chrI. We fluorescently labeled the terminus regions of chrI and chrII and followed their movements during the bacterial cell cycle. The chrI terminus behaved similarly to that of the Escherichia coli chromosome in that it segregated at the very end of the cell division cycle: cells showed a single fluorescent focus even when the division septum was nearly complete. In contrast, the single focus representing the chrII terminus could divide at the midcell position well before cell septation was conspicuous. There were also cells where the single focus for chrII lingered at midcell until the end of a division cycle, like the terminus of chrI. The single focus in these cells overlapped with the terminus focus for chrI in all cases. It appears that there could be coordination between the two chromosomes through the replication and/or segregation of the terminus region to ensure their segregation to daughter cells.

  18. The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation

    Directory of Open Access Journals (Sweden)

    Semin eLee

    2014-09-01

    Full Text Available The control of chromosome segregation relies on the spindle assembly checkpoint (SAC, a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling.

  19. Nuclear envelope expansion is crucial for proper chromosomal segregation during a closed mitosis.

    Science.gov (United States)

    Takemoto, Ai; Kawashima, Shigehiro A; Li, Juan-Juan; Jeffery, Linda; Yamatsugu, Kenzo; Elemento, Olivier; Nurse, Paul

    2016-03-15

    Here, we screened a 10,371 library of diverse molecules using a drug-sensitive fission yeast strain to identify compounds which cause defects in chromosome segregation during mitosis. We identified a phosphorium-ylide-based compound Cutin-1 which inhibits nuclear envelope expansion and nuclear elongation during the closed mitosis of fission yeast, and showed that its target is the β-subunit of fatty acid synthase. A point mutation in the dehydratase domain of Fas1 conferred in vivo and in vitro resistance to Cutin-1. Time-lapse photomicrography showed that the bulk of the chromosomes were only transiently separated during mitosis, and nucleoli separation was defective. Subsequently sister chromatids re-associated leading to chromosomal mis-segregation. These segregation defects were reduced when the nuclear volume was increased and were increased when the nuclear volume was reduced. We propose that there needs to be sufficient nuclear volume to allow the nuclear elongation necessary during a closed mitosis to take place for proper chromosome segregation, and that inhibition of fatty acid synthase compromises nuclear elongation and leads to defects in chromosomal segregation.

  20. Chromosome mis-segregation and cytokinesis failure in trisomic human cells.

    Science.gov (United States)

    Nicholson, Joshua M; Macedo, Joana C; Mattingly, Aaron J; Wangsa, Darawalee; Camps, Jordi; Lima, Vera; Gomes, Ana M; Dória, Sofia; Ried, Thomas; Logarinho, Elsa; Cimini, Daniela

    2015-05-05

    Cancer cells display aneuploid karyotypes and typically mis-segregate chromosomes at high rates, a phenotype referred to as chromosomal instability (CIN). To test the effects of aneuploidy on chromosome segregation and other mitotic phenotypes we used the colorectal cancer cell line DLD1 (2n = 46) and two variants with trisomy 7 or 13 (DLD1+7 and DLD1+13), as well as euploid and trisomy 13 amniocytes (AF and AF+13). We found that trisomic cells displayed higher rates of chromosome mis-segregation compared to their euploid counterparts. Furthermore, cells with trisomy 13 displayed a distinctive cytokinesis failure phenotype. We showed that up-regulation of SPG20 expression, brought about by trisomy 13 in DLD1+13 and AF+13 cells, is sufficient for the cytokinesis failure phenotype. Overall, our study shows that aneuploidy can induce chromosome mis-segregation. Moreover, we identified a trisomy 13-specific mitotic phenotype that is driven by up-regulation of a gene encoded on the aneuploid chromosome.

  1. A stochastic model of kinetochore-microtubule attachment accurately describes fission yeast chromosome segregation.

    Science.gov (United States)

    Gay, Guillaume; Courtheoux, Thibault; Reyes, Céline; Tournier, Sylvie; Gachet, Yannick

    2012-03-19

    In fission yeast, erroneous attachments of spindle microtubules to kinetochores are frequent in early mitosis. Most are corrected before anaphase onset by a mechanism involving the protein kinase Aurora B, which destabilizes kinetochore microtubules (ktMTs) in the absence of tension between sister chromatids. In this paper, we describe a minimal mathematical model of fission yeast chromosome segregation based on the stochastic attachment and detachment of ktMTs. The model accurately reproduces the timing of correct chromosome biorientation and segregation seen in fission yeast. Prevention of attachment defects requires both appropriate kinetochore orientation and an Aurora B-like activity. The model also reproduces abnormal chromosome segregation behavior (caused by, for example, inhibition of Aurora B). It predicts that, in metaphase, merotelic attachment is prevented by a kinetochore orientation effect and corrected by an Aurora B-like activity, whereas in anaphase, it is corrected through unbalanced forces applied to the kinetochore. These unbalanced forces are sufficient to prevent aneuploidy.

  2. Recruiting a microtubule-binding complex to DNA directs chromosome segregation in budding yeast

    OpenAIRE

    Murray, Andrew W.; Lacefield, Soni; Lau, Tsz Cham Derek

    2009-01-01

    Accurate chromosome segregation depends on the kinetochore, the complex of proteins that link microtubules to centromeric DNA1. The budding yeast kinetochore consists of more than 80 proteins assembled on a 125bp region of DNA1. We studied the assembly and function of kinetochore components by fusing individual kinetochore proteins to the lactose repressor (LacI) and testing their ability to improve the segregation of a plasmid carrying tandem repeats of the lactose operator (LacO). Targeting...

  3. DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation.

    Science.gov (United States)

    Pek, Jun Wei; Kai, Toshie

    2011-07-19

    During mitosis, faithful inheritance of genetic material is achieved by chromosome segregation, as mediated by the condensin I and II complexes. Failed chromosome segregation can result in neoplasm formation, infertility, and birth defects. Recently, the germ-line-specific DEAD-box RNA helicase Vasa was demonstrated to promote mitotic chromosome segregation in Drosophila by facilitating robust chromosomal localization of Barren (Barr), a condensin I component. This mitotic function of Vasa is mediated by Aubergine and Spindle-E, which are two germ-line components of the Piwi-interacting RNA pathway. Faithful segregation of chromosomes should be executed both in germ-line and somatic cells. However, whether a similar mechanism also functions in promoting chromosome segregation in somatic cells has not been elucidated. Here, we present evidence that belle (vasa paralog) and the RNA interference pathway regulate chromosome segregation in Drosophila somatic cells. During mitosis, belle promotes robust Barr chromosomal localization and chromosome segregation. Belle's localization to condensing chromosomes depends on dicer-2 and argonaute2. Coimmunoprecipitation experiments indicated that Belle interacts with Barr and Argonaute2 and is enriched at endogenous siRNA (endo-siRNA)-generating loci. Our results suggest that Belle functions in promoting chromosome segregation in Drosophila somatic cells via the endo-siRNA pathway. DDX3 (human homolog of belle) and DICER function in promoting chromosome segregation and hCAP-H (human homolog of Barr) localization in HeLa cells, indicating a conserved function for those proteins in human cells. Our results suggest that the RNA helicase Belle/DDX3 and the RNA interference pathway perform a common role in regulating chromosome segregation in Drosophila and human somatic cells.

  4. Meiosis I chromosome segregation is established through regulation of microtubule-kinetochore interactions.

    Science.gov (United States)

    Miller, Matthew P; Unal, Elçin; Brar, Gloria A; Amon, Angelika

    2012-12-18

    During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule-kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule-kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern.DOI:http://dx.doi.org/10.7554/eLife.00117.001.

  5. Functional Characterization of CENP-A Post-Translational Modifications in Chromosome Segregation

    Science.gov (United States)

    2014-07-01

    be conducted in year 2 and 3 of this proposal to deduce the relevance of this increased CENP-A methylation during the beginning of mitosis . To... mitosis and accurately segregate chromosomes. Overexpression of CENP-A leads to its mislocalisation and missegregation of chromosomes9. Similarly loss...centromeric chromatin requires exit from mitosis . The Journal of cell biology. 2007;176(6):795-805. 9. Tomonaga T, Matsushita K, Yamaguchi S, Oohashi T

  6. Role of the Number of Microtubules in Chromosome Segregation during Cell Division

    CERN Document Server

    Bertalan, Zsolt; La Porta, Caterina A M; Zapperi, Stefano

    2015-01-01

    Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compa...

  7. SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae

    NARCIS (Netherlands)

    Minnen, Anita; Attaiech, Laetitia; Thon, Maria; Gruber, Stephan; Veening, Jan-Willem

    2011-01-01

    Segregation of replicated chromosomes is an essential process in all organisms. How bacteria, such as the oval-shaped human pathogen Streptococcus pneumoniae, efficiently segregate their chromosomes is poorly understood. Here we show that the pneumococcal homologue of the DNA-binding protein ParB re

  8. Co-segregation of sex chromosomes in the male black widow spider Latrodectus mactans (Araneae, Theridiidae).

    Science.gov (United States)

    Ault, Jeffrey G; Felt, Kristen D; Doan, Ryan N; Nedo, Alexander O; Ellison, Cassondra A; Paliulis, Leocadia V

    2017-02-23

    During meiosis I, homologous chromosomes join together to form bivalents. Through trial and error, bivalents achieve stable bipolar orientations (attachments) on the spindle that eventually allow the segregation of homologous chromosomes to opposite poles. Bipolar orientations are stable through tension generated by poleward forces to opposite poles. Unipolar orientations lack tension and are stereotypically not stable. The behavior of sex chromosomes during meiosis I in the male black widow spider Latrodectus mactans (Araneae, Theridiidae) challenges the principles governing such a scenario. We found that male L. mactans has two distinct X chromosomes, X1 and X2. The X chromosomes join together to form a connection that is present in prometaphase I but is lost during metaphase I, before the autosomes disjoin at anaphase I. We found that both X chromosomes form stable unipolar orientations to the same pole that assure their co-segregation at anaphase I. Using micromanipulation, immunofluorescence microscopy, and electron microscopy, we studied this unusual chromosome behavior to explain how it may fit the current dogma of chromosome distribution during cell division.

  9. Oxidative stress in oocytes during midprophase induces premature loss of cohesion and chromosome segregation errors.

    Science.gov (United States)

    Perkins, Adrienne T; Das, Thomas M; Panzera, Lauren C; Bickel, Sharon E

    2016-11-01

    In humans, errors in meiotic chromosome segregation that produce aneuploid gametes increase dramatically as women age, a phenomenon termed the "maternal age effect." During meiosis, cohesion between sister chromatids keeps recombinant homologs physically attached and premature loss of cohesion can lead to missegregation of homologs during meiosis I. A growing body of evidence suggests that meiotic cohesion deteriorates as oocytes age and contributes to the maternal age effect. One hallmark of aging cells is an increase in oxidative damage caused by reactive oxygen species (ROS). Therefore, increased oxidative damage in older oocytes may be one of the factors that leads to premature loss of cohesion and segregation errors. To test this hypothesis, we used an RNAi strategy to induce oxidative stress in Drosophila oocytes and measured the fidelity of chromosome segregation during meiosis. Knockdown of either the cytoplasmic or mitochondrial ROS scavenger superoxide dismutase (SOD) caused a significant increase in segregation errors, and heterozygosity for an smc1 deletion enhanced this phenotype. FISH analysis indicated that SOD knockdown moderately increased the percentage of oocytes with arm cohesion defects. Consistent with premature loss of arm cohesion and destabilization of chiasmata, the frequency at which recombinant homologs missegregate during meiosis I is significantly greater in SOD knockdown oocytes than in controls. Together these results provide an in vivo demonstration that oxidative stress during meiotic prophase induces chromosome segregation errors and support the model that accelerated loss of cohesion in aging human oocytes is caused, at least in part, by oxidative damage.

  10. Conjugal plasmid transfer in Streptomyces resembles bacterial chromosome segregation by FtsK/SpoIIIE

    OpenAIRE

    Vogelmann, Jutta; Ammelburg, Moritz; Finger, Constanze; Guezguez, Jamil; LINKE, Dirk; Flötenmeyer, Matthias; Stierhof, York-Dieter; Wohlleben, Wolfgang; Muth, Günther

    2011-01-01

    Most bacteria share virulence and resistance genes by transferring single-stranded DNA through a type IV secretion system. Streptomycetes, however, exchange dsDNA, using a system found to closely resemble machineries for prokaryotic chromosome segregation or DNA translocation during spore formation.

  11. The ParB-parS Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae

    NARCIS (Netherlands)

    Attaiech, Laetitia; Minnen, Anita; Kjos, Morten; Gruber, Stephan; Veening, Jan-Willem

    2015-01-01

    UNLABELLED: ParB proteins bind centromere-like DNA sequences called parS sites and are involved in plasmid and chromosome segregation in bacteria. We previously showed that the opportunistic human pathogen Streptococcus pneumoniae contains four parS sequences located close to the origin of replicati

  12. Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2012-01-01

    Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer...

  13. Condensin II resolves chromosomal associations to enable anaphase I segregation in Drosophila male meiosis.

    Directory of Open Access Journals (Sweden)

    Tom A Hartl

    2008-10-01

    Full Text Available Several meiotic processes ensure faithful chromosome segregation to create haploid gametes. Errors to any one of these processes can lead to zygotic aneuploidy with the potential for developmental abnormalities. During prophase I of Drosophila male meiosis, each bivalent condenses and becomes sequestered into discrete chromosome territories. Here, we demonstrate that two predicted condensin II subunits, Cap-H2 and Cap-D3, are required to promote territory formation. In mutants of either subunit, territory formation fails and chromatin is dispersed throughout the nucleus. Anaphase I is also abnormal in Cap-H2 mutants as chromatin bridges are found between segregating heterologous and homologous chromosomes. Aneuploid sperm may be generated from these defects as they occur at an elevated frequency and are genotypically consistent with anaphase I segregation defects. We propose that condensin II-mediated prophase I territory formation prevents and/or resolves heterologous chromosomal associations to alleviate their potential interference in anaphase I segregation. Furthermore, condensin II-catalyzed prophase I chromosome condensation may be necessary to resolve associations between paired homologous chromosomes of each bivalent. These persistent chromosome associations likely consist of DNA entanglements, but may be more specific as anaphase I bridging was rescued by mutations in the homolog conjunction factor teflon. We propose that the consequence of condensin II mutations is a failure to resolve heterologous and homologous associations mediated by entangled DNA and/or homolog conjunction factors. Furthermore, persistence of homologous and heterologous interchromosomal associations lead to anaphase I chromatin bridging and the generation of aneuploid gametes.

  14. Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

    Science.gov (United States)

    Matsuhara, Hirotada; Yamamoto, Ayumu

    2016-01-01

    Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis.

  15. Connecting the dots of the bacterial cell cycle: Coordinating chromosome replication and segregation with cell division.

    Science.gov (United States)

    Hajduk, Isabella V; Rodrigues, Christopher D A; Harry, Elizabeth J

    2016-05-01

    Proper division site selection is crucial for the survival of all organisms. What still eludes us is how bacteria position their division site with high precision, and in tight coordination with chromosome replication and segregation. Until recently, the general belief, at least in the model organisms Bacillus subtilis and Escherichia coli, was that spatial regulation of division comes about by the combined negative regulatory mechanisms of the Min system and nucleoid occlusion. However, as we review here, these two systems cannot be solely responsible for division site selection and we highlight additional regulatory mechanisms that are at play. In this review, we put forward evidence of how chromosome replication and segregation may have direct links with cell division in these bacteria and the benefit of recent advances in chromosome conformation capture techniques in providing important information about how these three processes mechanistically work together to achieve accurate generation of progenitor cells.

  16. Segregation of an X ring chromosome in two generations.

    Science.gov (United States)

    Dallapiccola, B; Bruni, L; Boscherini, B; Pasquino, A M; Chessa, L; Vignetti, P

    1980-01-01

    A 45,X/46,X,r(X) mosaicism was found in a mother and daughter. Characterisation of the ring by banding studies showed that breakpoints had occurred at bands Xp13 and Xq27. It is confirmed that women heterozygotes for partial deficiencies of the short arm of an X chromosome are fertile. Although the mother developed secondary amenorrhoea at the age of 29, it is suggested that fertility per se may not be affected by deficiencies of the distal part of Xq. Images PMID:7205906

  17. Cell cycle coordination and regulation of bacterial chromosome segregation dynamics by polarly localized proteins.

    Science.gov (United States)

    Schofield, Whitman B; Lim, Hoong Chuin; Jacobs-Wagner, Christine

    2010-09-15

    What regulates chromosome segregation dynamics in bacteria is largely unknown. Here, we show in Caulobacter crescentus that the polarity factor TipN regulates the directional motion and overall translocation speed of the parS/ParB partition complex by interacting with ParA at the new pole. In the absence of TipN, ParA structures can regenerate behind the partition complex, leading to stalls and back-and-forth motions of parS/ParB, reminiscent of plasmid behaviour. This extrinsic regulation of the parS/ParB/ParA system directly affects not only division site selection, but also cell growth. Other mechanisms, including the pole-organizing protein PopZ, compensate for the defect in segregation regulation in ΔtipN cells. Accordingly, synthetic lethality of PopZ and TipN is caused by severe chromosome segregation and cell division defects. Our data suggest a mechanistic framework for adapting a self-organizing oscillator to create motion suitable for chromosome segregation.

  18. Structural and physical aspects of bacterial chromosome segregation.

    Science.gov (United States)

    Woldringh, Conrad L; Nanninga, Nanne

    2006-11-01

    Microscopic observations on the bacterial nucleoid suggest that the chromosome occurs in the cell as a compact nucleoid phase separate from the cytoplasm. Physical theory likewise predicts a phase separation, taking into consideration DNA supercoiling, nucleoid-binding proteins, and excluded-volume interactions between DNA and cytoplasmic proteins. Specific DNA loci, visualized as oriC-GFP spots in the densely packed nucleoid, exhibit a very low diffusion coefficient indicating that they are virtually immobile and may primarily be moved by overall length growth. Such gradual movement could be effectuated by replication, transertion (combined transcription, translation, and insertion of proteins), and actin- (MreB) directed surface synthesis. Differences in the movement and positioning of gene loci between Escherichia coli and Caulobacter crescentus are discussed. We propose that a low diffusion coefficient could explain the linear positioning of genes in the nucleoid and that differential transcriptional activity could induce different mobilities between either replichores (E. coli) or daughter strands (C. crescentus). The transertion process, possibly in combination with MreB cytoskeletal tracks, could overcome the compaction forces and move specific chromosomal regions and the nucleoid as a whole without invoking a dedicated mechanism.

  19. The cohesion stabilizer sororin favors DNA repair and chromosome segregation during mouse oocyte meiosis.

    Science.gov (United States)

    Huang, Chun-Jie; Yuan, Yi-Feng; Wu, Di; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Huo, Li-Jun

    2017-03-01

    Maintenance and timely termination of cohesion on chromosomes ensures accurate chromosome segregation to guard against aneuploidy in mammalian oocytes and subsequent chromosomally abnormal pregnancies. Sororin, a cohesion stabilizer whose relevance in antagonizing the anti-cohesive property of Wings-apart like protein (Wapl), has been characterized in mitosis; however, the role of Sororin remains unclear during mammalian oocyte meiosis. Here, we show that Sororin is required for DNA damage repair and cohesion maintenance on chromosomes, and consequently, for mouse oocyte meiotic program. Sororin is constantly expressed throughout meiosis and accumulates on chromatins at germinal vesicle (GV) stage/G2 phase. It localizes onto centromeres from germinal vesicle breakdown (GVBD) to metaphase II stage. Inactivation of Sororin compromises the GVBD and first polar body extrusion (PBE). Furthermore, Sororin inactivation induces DNA damage indicated by positive γH2AX foci in GV oocytes and precocious chromatin segregation in MII oocytes. Finally, our data indicate that PlK1 and MPF dissociate Sororin from chromosome arms without affecting its centromeric localization. Our results define Sororin as a determinant during mouse oocyte meiotic maturation by favoring DNA damage repair and chromosome separation, and thereby, maintaining the genome stability and generating haploid gametes.

  20. The multiple roles of Bub1 in chromosome segregation during mitosis and meiosis

    Energy Technology Data Exchange (ETDEWEB)

    Marchetti, Francesco; Venkatachalam, Sundaresan

    2009-06-19

    Aneuploidy, any deviation from an exact multiple of the haploid number of chromosomes, is a common occurrence in cancer and represents the most frequent chromosomal disorder in newborns. Eukaryotes have evolved mechanisms to assure the fidelity of chromosome segregation during cell division that include a multiplicity of checks and controls. One of the main cell division control mechanisms is the spindle assembly checkpoint (SAC) that monitors the proper attachment of chromosomes to spindle fibers and prevents anaphase until all kinetochores are properly attached. The mammalian SAC is composed by at least 14 evolutionary-conserved proteins that work in a coordinated fashion to monitor the establishment of amphitelic attachment of all chromosomes before allowing cell division to occur. Among the SAC proteins, the budding uninhibited by benzimidazole protein 1 (Bub1), is a highly conserved protein of prominent importance for the proper functioning of the SAC. Studies have revealed many roles for Bub1 in both mitosis and meiosis, including the localization of other SAC proteins to the kinetochore, SAC signaling, metaphase congression and the protection of the sister chromatid cohesion. Recent data show striking sex specific differences in the response to alterations in Bub1 activity. Proper Bub1 functioning is particularly important during oogenesis in preventing the generation of aneuploid gametes that can have detrimental effects on the health status of the fetus and the newborn. These data suggest that Bub1 is a master regulator of SAC and chromosomal segregation in both mitosis and meiosis. Elucidating its many essential functions in regulating proper chromosome segregation can have important consequences for preventing tumorigenesis and developmental abnormalities.

  1. Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation.

    Science.gov (United States)

    Chen, Jun-Song; Lu, Lucy X; Ohi, Melanie D; Creamer, Kevin M; English, Chauca; Partridge, Janet F; Ohi, Ryoma; Gould, Kathleen L

    2011-11-14

    Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore-MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k-MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1-Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1-Dlc1 complex in regulating the k-MT interface and chromosome segregation.

  2. Tumor-specific chromosome mis-segregation controls cancer plasticity by maintaining tumor heterogeneity.

    Directory of Open Access Journals (Sweden)

    Yuanjie Hu

    Full Text Available Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7 copy number variation (CNV in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers.

  3. Noc protein binds to specific DNA sequences to coordinate cell division with chromosome segregation.

    Science.gov (United States)

    Wu, Ling Juan; Ishikawa, Shu; Kawai, Yoshikazu; Oshima, Taku; Ogasawara, Naotake; Errington, Jeff

    2009-07-08

    Coordination of chromosome segregation and cytokinesis is crucial for efficient cell proliferation. In Bacillus subtilis, the nucleoid occlusion protein Noc protects the chromosomes by associating with the chromosome and preventing cell division in its vicinity. Using protein localization, ChAP-on-Chip and bioinformatics, we have identified a consensus Noc-binding DNA sequence (NBS), and have shown that Noc is targeted to about 70 discrete regions scattered around the chromosome, though absent from a large region around the replication terminus. Purified Noc bound specifically to an NBS in vitro. NBSs inserted near the replication terminus bound Noc-YFP and caused a delay in cell division. An autonomous plasmid carrying an NBS array recruited Noc-YFP and conferred a severe Noc-dependent inhibition of cell division. This shows that Noc is a potent inhibitor of division, but that its activity is strictly localized by the interaction with NBS sites in vivo. We propose that Noc serves not only as a spatial regulator of cell division to protect the nucleoid, but also as a timing device with an important role in the coordination of chromosome segregation and cell division.

  4. Generation of meiomaps of genome-wide recombination and chromosome segregation in human oocytes

    DEFF Research Database (Denmark)

    Ottolini, Christian S; Capalbo, Antonio; Newnham, Louise

    2016-01-01

    We have developed a protocol for the generation of genome-wide maps (meiomaps) of recombination and chromosome segregation for the three products of human female meiosis: the first and second polar bodies (PB1 and PB2) and the corresponding oocyte. PB1 is biopsied and the oocyte is artificially......-nucleotide polymorphisms (SNPs) genome-wide by microarray. Informative maternal heterozygous SNPs are phased using a haploid PB2 or oocyte as a reference. A simple algorithm is then used to identify the maternal haplotypes for each chromosome, in all of the products of meiosis for each oocyte. This allows mapping...

  5. Balanced Activity of Three Mitotic Motors Is Required for Bipolar Spindle Assembly and Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Roy G.H.P. van Heesbeen

    2014-08-01

    Full Text Available Bipolar spindle assembly requires force to organize the microtubule network. Here, we show that three motor proteins, namely Eg5, Kif15, and dynein, act together to produce the right force balance in the spindle. Excessive inward force results in monopolar spindle formation, while excessive outward force generation results in unstable spindles with splayed spindle poles. Blocking activity of all three motors prevents bipolar spindle formation, but established bipolar spindles are refractory to loss of all motor activity. Further analysis shows that although these preformed spindles remain bipolar, outward force generation is required to establish sufficient tension on kinetochores and to accomplish successful chromosome segregation. Together, these results show how Eg5, Kif15, and dynein work together to build a bipolar spindle and reveal an important role for antagonistic motors in chromosome segregation.

  6. A stochastic model of kinetochore–microtubule attachment accurately describes fission yeast chromosome segregation

    OpenAIRE

    Gay, Guillaume; Courtheoux, Thibault; Reyes, Céline; Tournier, Sylvie; Gachet, Yannick

    2012-01-01

    In fission yeast, erroneous attachments of spindle microtubules to kinetochores are frequent in early mitosis. Most are corrected before anaphase onset by a mechanism involving the protein kinase Aurora B, which destabilizes kinetochore microtubules (ktMTs) in the absence of tension between sister chromatids. In this paper, we describe a minimal mathematical model of fission yeast chromosome segregation based on the stochastic attachment and detachment of ktMTs. The model accurately reproduce...

  7. Identification of Conserved MEL-28/ELYS Domains with Essential Roles in Nuclear Assembly and Chromosome Segregation.

    Directory of Open Access Journals (Sweden)

    Georgina Gómez-Saldivar

    2016-06-01

    Full Text Available Nucleoporins are the constituents of nuclear pore complexes (NPCs and are essential regulators of nucleocytoplasmic transport, gene expression and genome stability. The nucleoporin MEL-28/ELYS plays a critical role in post-mitotic NPC reassembly through recruitment of the NUP107-160 subcomplex, and is required for correct segregation of mitotic chromosomes. Here we present a systematic functional and structural analysis of MEL-28 in C. elegans early development and human ELYS in cultured cells. We have identified functional domains responsible for nuclear envelope and kinetochore localization, chromatin binding, mitotic spindle matrix association and chromosome segregation. Surprisingly, we found that perturbations to MEL-28's conserved AT-hook domain do not affect MEL-28 localization although they disrupt MEL-28 function and delay cell cycle progression in a DNA damage checkpoint-dependent manner. Our analyses also uncover a novel meiotic role of MEL-28. Together, these results show that MEL-28 has conserved structural domains that are essential for its fundamental roles in NPC assembly and chromosome segregation.

  8. Chromosome segregation impacts on cell growth and division site selection in Corynebacterium glutamicum.

    Science.gov (United States)

    Donovan, Catriona; Schauss, Astrid; Krämer, Reinhard; Bramkamp, Marc

    2013-01-01

    Spatial and temporal regulation of bacterial cell division is imperative for the production of viable offspring. In many rod-shaped bacteria, regulatory systems such as the Min system and nucleoid occlusion ensure the high fidelity of midcell divisome positioning. However, regulation of division site selection in bacteria lacking recognizable Min and nucleoid occlusion remains less well understood. Here, we describe one such rod-shaped organism, Corynebacterium glutamicum, which does not always place the division septum precisely at midcell. Here we now show at single cell level that cell growth and division site selection are spatially and temporally regulated by chromosome segregation. Mutants defective in chromosome segregation have more variable cell growth and aberrant placement of the division site. In these mutants, division septa constrict over and often guillotine the nucleoid, leading to nonviable, DNA-free cells. Our results suggest that chromosome segregation or some nucleoid associated factor influences growth and division site selection in C. glutamicum. Understanding growth and regulation of C. glutamicum cells will also be of importance to develop strains for industrial production of biomolecules, such as amino acids.

  9. Chromosome segregation impacts on cell growth and division site selection in Corynebacterium glutamicum.

    Directory of Open Access Journals (Sweden)

    Catriona Donovan

    Full Text Available Spatial and temporal regulation of bacterial cell division is imperative for the production of viable offspring. In many rod-shaped bacteria, regulatory systems such as the Min system and nucleoid occlusion ensure the high fidelity of midcell divisome positioning. However, regulation of division site selection in bacteria lacking recognizable Min and nucleoid occlusion remains less well understood. Here, we describe one such rod-shaped organism, Corynebacterium glutamicum, which does not always place the division septum precisely at midcell. Here we now show at single cell level that cell growth and division site selection are spatially and temporally regulated by chromosome segregation. Mutants defective in chromosome segregation have more variable cell growth and aberrant placement of the division site. In these mutants, division septa constrict over and often guillotine the nucleoid, leading to nonviable, DNA-free cells. Our results suggest that chromosome segregation or some nucleoid associated factor influences growth and division site selection in C. glutamicum. Understanding growth and regulation of C. glutamicum cells will also be of importance to develop strains for industrial production of biomolecules, such as amino acids.

  10. Sex ratio in normal and disomic sperm: Evidence that the extra chromosome 21 preferentially segregates with the Y chromosome

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, D.K.; Millie, E.A.; Hassold, T.J. [Case Western Univ., Cleveland, OH (United States)]|[Univ. Hospitals of Cleveland, OH (United States)] [and others

    1996-11-01

    In humans, deviations from a 1:1 male:female ratio have been identified in both chromosomally normal and trisomic live births: among normal newborns there is a slight excess of males, among trisomy 18 live borns a large excess of females, and among trisomy 21 live borns an excess of males. These differences could arise from differential production of or fertilization by Y- or X-bearing sperm or from selection against male or female conceptions. To examine the proportion of Y- and X- bearing sperm in normal sperm and in sperm disomic for chromosomes 18 or 21, we used three-color FISH (to the X and Y and either chromosome 18 or chromosome 21) to analyze > 300,000 sperm from 24 men. In apparently normal sperm, the sex ratio was nearly 1:1 (148,074 Y-bearing to 148,657 X-bearing sperm), and the value was not affected by the age of the donor. Certain of the donors, however, had significant excesses of Y- or X-bearing sperm. In disomy 18 sperm, there were virtually identical numbers of Y- and X-bearing sperm; thus, the excess of females in trisomy 18 presumably is due to selection against male trisomic conceptions. In contrast, we observed 69 Y-bearing and 44 X-bearing sperm disomic for chromosome 21. This is consistent with previous molecular studies, which have identified an excess of males among paternally derived cases of trisomy 21, and suggests that some of the excess of males among Down syndrome individuals is attributable to a nondisjunctional mechanism in which the extra chromosome 21 preferentially segregates with the Y chromosome. 17 refs., 2 tabs.

  11. SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae

    OpenAIRE

    Minnen, Anita; Attaiech, Laetitia; Thon, Maria; Gruber, Stephan; Veening, Jan-Willem

    2011-01-01

    Segregation of replicated chromosomes is an essential process in all organisms. How bacteria, such as the oval-shaped human pathogen Streptococcus pneumoniae, efficiently segregate their chromosomes is poorly understood. Here we show that the pneumococcal homologue of the DNA-binding protein ParB recruits S. pneumoniae condensin (SMC) to centromere-like DNA sequences (parS) that are located near the origin of replication, in a similar fashion as was shown for the rod-shaped model bacterium Ba...

  12. Nuclear actin-related protein is required for chromosome segregation in Toxoplasma gondii.

    Science.gov (United States)

    Suvorova, Elena S; Lehmann, Margaret M; Kratzer, Stella; White, Michael W

    2012-01-01

    Apicomplexa parasites use complex cell cycles to replicate that are not well understood mechanistically. We have established a robust forward genetic strategy to identify the essential components of parasite cell division. Here we describe a novel temperature sensitive Toxoplasma strain, mutant 13-20C2, which growth arrests due to a defect in mitosis. The primary phenotype is the mis-segregation of duplicated chromosomes with chromosome loss during nuclear division. This defect is conditional-lethal with respect to temperature, although relatively mild in regard to the preservation of the major microtubule organizing centers. Despite severe DNA loss many of the physical structures associated with daughter budding and the assembly of invasion structures formed and operated normally at the non-permissive temperature before completely arresting. These results suggest there are coordinating mechanisms that govern the timing of these events in the parasite cell cycle. The defect in mutant 13-20C2 was mapped by genetic complementation to Toxoplasma chromosome III and to a specific mutation in the gene encoding an ortholog of nuclear actin-related protein 4. A change in a conserved isoleucine to threonine in the helical structure of this nuclear actin related protein leads to protein instability and cellular mis-localization at the higher temperature. Given the age of this protist family, the results indicate a key role for nuclear actin-related proteins in chromosome segregation was established very early in the evolution of eukaryotes.

  13. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Melissa [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States); Peddibhotla, Sirisha [Department of Molecular and Human Genetics, Baylor College of Medicine, John P. McGovern Campus, NABS-0250, Houston, TX 77030 (United States); McHenry, Peter [Department of Biology, Southwestern Adventist University, 100 W. Hillcrest, Keene, TX 76059 (United States); Chang, Peggy; Yochum, Zachary; Park, Ko Un; Sears, James Cooper; Vargo-Gogola, Tracy, E-mail: vargo-gogola.1@nd.edu [Department of Biochemistry and Molecular Biology and the Indiana University Simon Cancer Center, Indiana University School of Medicine, 1234 Notre Dame Avenue, South Bend, IN 46617 (United States)

    2012-04-25

    Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP) deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis.

  14. CDE-1 affects chromosome segregation through uridylation of CSR-1-bound siRNAs.

    Science.gov (United States)

    van Wolfswinkel, Josien C; Claycomb, Julie M; Batista, Pedro J; Mello, Craig C; Berezikov, Eugene; Ketting, René F

    2009-10-02

    We have studied the function of a conserved germline-specific nucleotidyltransferase protein, CDE-1, in RNAi and chromosome segregation in C. elegans. CDE-1 localizes specifically to mitotic chromosomes in embryos. This localization requires the RdRP EGO-1, which physically interacts with CDE-1, and the Argonaute protein CSR-1. We found that CDE-1 is required for the uridylation of CSR-1 bound siRNAs, and that in the absence of CDE-1 these siRNAs accumulate to inappropriate levels, accompanied by defects in both meiotic and mitotic chromosome segregation. Elevated siRNA levels are associated with erroneous gene silencing, most likely through the inappropriate loading of CSR-1 siRNAs into other Argonaute proteins. We propose a model in which CDE-1 restricts specific EGO-1-generated siRNAs to the CSR-1 mediated, chromosome associated RNAi pathway, thus separating it from other endogenous RNAi pathways. The conserved nature of CDE-1 suggests that similar sorting mechanisms may operate in other animals, including mammals.

  15. Chromosome segregation in Archaea mediated by a hybrid DNA partition machine.

    Science.gov (United States)

    Kalliomaa-Sanford, Anne K; Rodriguez-Castañeda, Fernando A; McLeod, Brett N; Latorre-Roselló, Victor; Smith, Jasmine H; Reimann, Julia; Albers, Sonja V; Barillà, Daniela

    2012-03-06

    Eukarya and, more recently, some bacteria have been shown to rely on a cytoskeleton-based apparatus to drive chromosome segregation. In contrast, the factors and mechanisms underpinning this fundamental process are underexplored in archaea, the third domain of life. Here we establish that the archaeon Sulfolobus solfataricus harbors a hybrid segrosome consisting of two interacting proteins, SegA and SegB, that play a key role in genome segregation in this organism. SegA is an ortholog of bacterial, Walker-type ParA proteins, whereas SegB is an archaea-specific factor lacking sequence identity to either eukaryotic or bacterial proteins, but sharing homology with a cluster of uncharacterized factors conserved in both crenarchaea and euryarchaea, the two major archaeal sub-phyla. We show that SegA is an ATPase that polymerizes in vitro and that SegB is a site-specific DNA-binding protein contacting palindromic sequences located upstream of the segAB cassette. SegB interacts with SegA in the presence of nucleotides and dramatically affects its polymerization dynamics. Our data demonstrate that SegB strongly stimulates SegA polymerization, possibly by promoting SegA nucleation and accelerating polymer growth. Increased expression levels of segAB resulted in severe growth and chromosome segregation defects, including formation of anucleate cells, compact nucleoids confined to one half of the cell compartment and fragmented nucleoids. The overall picture emerging from our findings indicates that the SegAB complex fulfills a crucial function in chromosome segregation and is the prototype of a DNA partition machine widespread across archaea.

  16. Chromosome segregation analysis in human embryos obtained from couples involving male carriers of reciprocal or Robertsonian translocation.

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz

    Full Text Available The objective of this study was to investigate the frequency and type of chromosome segregation patterns in cleavage stage embryos obtained from male carriers of Robertsonian (ROB and reciprocal (REC translocations undergoing preimplantation genetic diagnosis (PGD at our reproductive center. We used FISH to analyze chromosome segregation in 308 day 3 cleavage stage embryos obtained from 26 patients. The percentage of embryos consistent with normal or balanced segregation (55.1% vs. 27.1% and clinical pregnancy (62.5% vs. 19.2% rates were higher in ROB than the REC translocation carriers. Involvement of non-acrocentric chromosome(s or terminal breakpoint(s in reciprocal translocations was associated with an increase in the percent of embryos consistent with adjacent 1 but with a decrease in 3∶1 segregation. Similar results were obtained in the analysis of nontransferred embryos donated for research. 3∶1 segregation was the most frequent segregation type in both day 3 (31% and spare (35% embryos obtained from carriers of t(11;22(q23;q11, the only non-random REC with the same breakpoint reported in a large number of unrelated families mainly identified by the birth of a child with derivative chromosome 22. These results suggest that chromosome segregation patterns in day 3 and nontransferred embryos obtained from male translocation carriers vary with the type of translocation and involvement of acrocentric chromosome(s or terminal breakpoint(s. These results should be helpful in estimating reproductive success in translocation carriers undergoing PGD.

  17. Overlapping two self-avoiding polymers in a closed cylindrical pore: Implications for chromosome segregation in a bacterial cell

    Science.gov (United States)

    Jung, Youngkyun; Ha, Bae-Yeun

    2010-11-01

    We study the spatial organization and segregation of two self-avoiding polymers trapped inside a closed cylindrical pore. Using molecular-dynamics simulations, we show how confinement shapes the chains, especially their mutual (entropic) force, chain miscibility, and segregation dynamics. Under strong confinement, the chains are shown to repel more strongly and thus segregate better if they are shorter and the confining space is more asymmetric, in contrast to the spherically confined case, where nonlinear chain topology is required for chain partitioning in equilibrium. When applied to bacterial chromosomes, our results imply that chromosome miscibility depends on how they are compacted and structured inside the cell (by proteins and supercoiling). Finally, longitudinal confinement is shown to have nontrivial effects on segregation dynamics by randomizing and thus slowing down the segregation process, which would otherwise be assisted with entropic forces.

  18. SCF ensures meiotic chromosome segregation through a resolution of meiotic recombination intermediates.

    Directory of Open Access Journals (Sweden)

    Shin-ya Okamoto

    Full Text Available The SCF (Skp1-Cul1-F-box complex contributes to a variety of cellular events including meiotic cell cycle control, but its function during meiosis is not understood well. Here we describe a novel function of SCF/Skp1 in meiotic recombination and subsequent chromosome segregation. The skp1 temperature-sensitive mutant exhibited abnormal distribution of spindle microtubules in meiosis II, which turned out to originate from abnormal bending of the spindle in meiosis I. Bent spindles were reported in mitosis of this mutant, but it remained unknown how SCF could affect spindle morphology. We found that the meiotic bent spindle in skp1 cells was due to a hypertension generated by chromosome entanglement. The spindle bending was suppressed by inhibiting double strand break (DSB formation, indicating that the entanglement was generated by the meiotic recombination machinery. Consistently, Rhp51/Rad51-Rad22/Rad52 foci persisted until meiosis I in skp1 cells, proving accumulation of recombination intermediates. Intriguingly bent spindles were also observed in the mutant of Fbh1, an F-box protein containing the DNA helicase domain, which is involved in meiotic recombination. Genetic evidence suggested its cooperation with SCF/Skp1. Thus, SCF/Skp1 together with Fbh1 is likely to function in the resolution of meiotic recombination intermediates, thereby ensuring proper chromosome segregation.

  19. Bub3 is a spindle assembly checkpoint protein regulating chromosome segregation during mouse oocyte meiosis.

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    Mo Li

    Full Text Available In mitosis, the spindle assembly checkpoint (SAC prevents anaphase onset until all chromosomes have been attached to the spindle microtubules and aligned correctly at the equatorial metaphase plate. The major checkpoint proteins in mitosis consist of mitotic arrest-deficient (Mad1-3, budding uninhibited by benzimidazole (Bub1, Bub3, and monopolar spindle 1(Mps1. During meiosis, for the formation of a haploid gamete, two consecutive rounds of chromosome segregation occur with only one round of DNA replication. To pull homologous chromosomes to opposite spindle poles during meiosis I, both sister kinetochores of a homologue must face toward the same pole which is very different from mitosis and meiosis II. As a core member of checkpoint proteins, the individual role of Bub3 in mammalian oocyte meiosis is unclear. In this study, using overexpression and RNA interference (RNAi approaches, we analyzed the role of Bub3 in mouse oocyte meiosis. Our data showed that overexpressed Bub3 inhibited meiotic metaphase-anaphase transition by preventing homologous chromosome and sister chromatid segregations in meiosis I and II, respectively. Misaligned chromosomes, abnormal polar body and double polar bodies were observed in Bub3 knock-down oocytes, causing aneuploidy. Furthermore, through cold treatment combined with Bub3 overexpression, we found that overexpressed Bub3 affected the attachments of microtubules and kinetochores during metaphase-anaphase transition. We propose that as a member of SAC, Bub3 is required for regulation of both meiosis I and II, and is potentially involved in kinetochore-microtubule attachment in mammalian oocytes.

  20. Prokaryotic ParA-ParB-parS system links bacterial chromosome segregation with the cell cycle.

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    Mierzejewska, Jolanta; Jagura-Burdzy, Grażyna

    2012-01-01

    While the essential role of episomal par loci in plasmid DNA partitioning has long been appreciated, the function of chromosomally encoded par loci is less clear. The chromosomal parA-parB genes are conserved throughout the bacterial kingdom and encode proteins homologous to those of the plasmidic Type I active partitioning systems. The third conserved element, the centromere-like sequence called parS, occurs in several copies in the chromosome. Recent studies show that the ParA-ParB-parS system is a key player of a mitosis-like process ensuring proper intracellular localization of certain chromosomal regions such as oriC domain and their active and directed segregation. Moreover, the chromosomal par systems link chromosome segregation with initiation of DNA replication and the cell cycle.

  1. Regulatory cross-talk links Vibrio cholerae chromosome II replication and segregation.

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    Yoshiharu Yamaichi

    2011-07-01

    Full Text Available There is little knowledge of factors and mechanisms for coordinating bacterial chromosome replication and segregation. Previous studies have revealed that genes (and their products that surround the origin of replication (oriCII of Vibrio cholerae chromosome II (chrII are critical for controlling the replication and segregation of this chromosome. rctB, which flanks one side of oriCII, encodes a protein that initiates chrII replication; rctA, which flanks the other side of oriCII, inhibits rctB activity. The chrII parAB2 operon, which is essential for chrII partitioning, is located immediately downstream of rctA. Here, we explored how rctA exerts negative control over chrII replication. Our observations suggest that RctB has at least two DNA binding domains--one for binding to oriCII and initiating replication and the other for binding to rctA and thereby inhibiting RctB's ability to initiate replication. Notably, the inhibitory effect of rctA could be alleviated by binding of ParB2 to a centromere-like parS site within rctA. Furthermore, by binding to rctA, ParB2 and RctB inversely regulate expression of the parAB2 genes. Together, our findings suggest that fluctuations in binding of the partitioning protein ParB2 and the chrII initiator RctB to rctA underlie a regulatory network controlling both oriCII firing and the production of the essential chrII partitioning proteins. Thus, by binding both RctB and ParB2, rctA serves as a nexus for regulatory cross-talk coordinating chrII replication and segregation.

  2. Regulatory cross-talk links Vibrio cholerae chromosome II replication and segregation.

    Science.gov (United States)

    Yamaichi, Yoshiharu; Gerding, Matthew A; Davis, Brigid M; Waldor, Matthew K

    2011-07-01

    There is little knowledge of factors and mechanisms for coordinating bacterial chromosome replication and segregation. Previous studies have revealed that genes (and their products) that surround the origin of replication (oriCII) of Vibrio cholerae chromosome II (chrII) are critical for controlling the replication and segregation of this chromosome. rctB, which flanks one side of oriCII, encodes a protein that initiates chrII replication; rctA, which flanks the other side of oriCII, inhibits rctB activity. The chrII parAB2 operon, which is essential for chrII partitioning, is located immediately downstream of rctA. Here, we explored how rctA exerts negative control over chrII replication. Our observations suggest that RctB has at least two DNA binding domains--one for binding to oriCII and initiating replication and the other for binding to rctA and thereby inhibiting RctB's ability to initiate replication. Notably, the inhibitory effect of rctA could be alleviated by binding of ParB2 to a centromere-like parS site within rctA. Furthermore, by binding to rctA, ParB2 and RctB inversely regulate expression of the parAB2 genes. Together, our findings suggest that fluctuations in binding of the partitioning protein ParB2 and the chrII initiator RctB to rctA underlie a regulatory network controlling both oriCII firing and the production of the essential chrII partitioning proteins. Thus, by binding both RctB and ParB2, rctA serves as a nexus for regulatory cross-talk coordinating chrII replication and segregation.

  3. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis.

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    Shin, Yong-Hyun; Choi, Youngsok; Erdin, Serpil Uckac; Yatsenko, Svetlana A; Kloc, Malgorzata; Yang, Fang; Wang, P Jeremy; Meistrich, Marvin L; Rajkovic, Aleksandar

    2010-11-04

    Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1(-/) (-)) testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1(-/) (-) testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/) (-) ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1(-/) (-) oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

  4. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis.

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    Yong-Hyun Shin

    2010-11-01

    Full Text Available Meiosis is unique to germ cells and essential for reproduction. During the first meiotic division, homologous chromosomes pair, recombine, and form chiasmata. The homologues connect via axial elements and numerous transverse filaments to form the synaptonemal complex. The synaptonemal complex is a critical component for chromosome pairing, segregation, and recombination. We previously identified a novel germ cell-specific HORMA domain encoding gene, Hormad1, a member of the synaptonemal complex and a mammalian counterpart to the yeast meiotic HORMA domain protein Hop1. Hormad1 is essential for mammalian gametogenesis as knockout male and female mice are infertile. Hormad1 deficient (Hormad1(-/ (- testes exhibit meiotic arrest in the early pachytene stage, and synaptonemal complexes cannot be visualized by electron microscopy. Hormad1 deficiency does not affect localization of other synaptonemal complex proteins, SYCP2 and SYCP3, but disrupts homologous chromosome pairing. Double stranded break formation and early recombination events are disrupted in Hormad1(-/ (- testes and ovaries as shown by the drastic decrease in the γH2AX, DMC1, RAD51, and RPA foci. HORMAD1 co-localizes with γH2AX to the sex body during pachytene. BRCA1, ATR, and γH2AX co-localize to the sex body and participate in meiotic sex chromosome inactivation and transcriptional silencing. Hormad1 deficiency abolishes γH2AX, ATR, and BRCA1 localization to the sex chromosomes and causes transcriptional de-repression on the X chromosome. Unlike testes, Hormad1(-/ (- ovaries have seemingly normal ovarian folliculogenesis after puberty. However, embryos generated from Hormad1(-/ (- oocytes are hyper- and hypodiploid at the 2 cell and 8 cell stage, and they arrest at the blastocyst stage. HORMAD1 is therefore a critical component of the synaptonemal complex that affects synapsis, recombination, and meiotic sex chromosome inactivation and transcriptional silencing.

  5. P190B RhoGAP Regulates Chromosome Segregation in Cancer Cells

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    Tracy Vargo-Gogola

    2012-04-01

    Full Text Available Rho GTPases are overexpressed and hyperactivated in many cancers, including breast cancer. Rho proteins, as well as their regulators and effectors, have been implicated in mitosis, and their altered expression promotes mitotic defects and aneuploidy. Previously, we demonstrated that p190B Rho GTPase activating protein (RhoGAP deficiency inhibits ErbB2-induced mammary tumor formation in mice. Here we describe a novel role for p190B as a regulator of mitosis. We found that p190B localized to centrosomes during interphase and mitosis, and that it is differentially phosphorylated during mitosis. Knockdown of p190B expression in MCF-7 and Hela cells increased the incidence of aberrant microtubule-kinetochore attachments at metaphase, lagging chromosomes at anaphase, and micronucleation, all of which are indicative of aneuploidy. Cell cycle analysis of p190B deficient MCF-7 cells revealed a significant increase in apoptotic cells with a concomitant decrease in cells in G1 and S phase, suggesting that p190B deficient cells die at the G1 to S transition. Chemical inhibition of the Rac GTPase during mitosis reduced the incidence of lagging chromosomes in p190B knockdown cells to levels detected in control cells, suggesting that aberrant Rac activity in the absence of p190B promotes chromosome segregation defects. Taken together, these data suggest that p190B regulates chromosome segregation and apoptosis in cancer cells. We propose that disruption of mitosis may be one mechanism by which p190B deficiency inhibits tumorigenesis.

  6. Synchronizing chromosome segregation by flux-dependent force equalization at kinetochores.

    Science.gov (United States)

    Matos, Irina; Pereira, António J; Lince-Faria, Mariana; Cameron, Lisa A; Salmon, Edward D; Maiato, Helder

    2009-07-13

    The synchronous movement of chromosomes during anaphase ensures their correct inheritance in every cell division. This reflects the uniformity of spindle forces acting on chromosomes and their simultaneous entry into anaphase. Although anaphase onset is controlled by the spindle assembly checkpoint, it remains unknown how spindle forces are uniformly distributed among different chromosomes. In this paper, we show that tension uniformity at metaphase kinetochores and subsequent anaphase synchrony in Drosophila S2 cells are promoted by spindle microtubule flux. These results can be explained by a mechanical model of the spindle where microtubule poleward translocation events associated with flux reflect relaxation of the kinetochore-microtubule interface, which accounts for the redistribution and convergence of kinetochore tensions in a timescale comparable to typical metaphase duration. As predicted by the model, experimental acceleration of mitosis precludes tension equalization and anaphase synchrony. We propose that flux-dependent equalization of kinetochore tensions ensures a timely and uniform maturation of kinetochore-microtubule interfaces necessary for error-free and coordinated segregation of chromosomes in anaphase.

  7. Spindle checkpoint-independent inhibition of mitotic chromosome segregation by Drosophila Mps1.

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    Althoff, Friederike; Karess, Roger E; Lehner, Christian F

    2012-06-01

    Monopolar spindle 1 (Mps1) is essential for the spindle assembly checkpoint (SAC), which prevents anaphase onset in the presence of misaligned chromosomes. Moreover, Mps1 kinase contributes in a SAC-independent manner to the correction of erroneous initial attachments of chromosomes to the spindle. Our characterization of the Drosophila homologue reveals yet another SAC-independent role. As in yeast, modest overexpression of Drosophila Mps1 is sufficient to delay progression through mitosis during metaphase, even though chromosome congression and metaphase alignment do not appear to be affected. This delay in metaphase depends on the SAC component Mad2. Although Mps1 overexpression in mad2 mutants no longer causes a metaphase delay, it perturbs anaphase. Sister kinetochores barely move apart toward spindle poles. However, kinetochore movements can be restored experimentally by separase-independent resolution of sister chromatid cohesion. We propose therefore that Mps1 inhibits sister chromatid separation in a SAC-independent manner. Moreover, we report unexpected results concerning the requirement of Mps1 dimerization and kinase activity for its kinetochore localization in Drosophila. These findings further expand Mps1's significance for faithful mitotic chromosome segregation and emphasize the importance of its careful regulation.

  8. Identification and cloning of the CHL4 gene controlling chromosome segregation in yeast.

    Science.gov (United States)

    Kouprina, N; Kirillov, A; Kroll, E; Koryabin, M; Shestopalov, B; Bannikov, V; Zakharyev, V; Larionov, V

    1993-10-01

    A collection of chl mutants characterized by decreased fidelity of chromosome transmission and by minichromosome nondisjunction in mitosis was examined for the ability to maintain nonessential dicentric plasmids. In one of the seven mutants analyzed, chl4, dicentric plasmids did not depress cell division. Moreover, nonessential dicentric plasmids were maintained stably without any rearrangements during many generations in the chl4 mutant. The rate of mitotic heteroallelic recombination in the chl4 mutant was not increased compared to that in an isogenic wild-type strain. Analysis of the segregation of a marked chromosome indicated that sister chromatid nondisjunction and sister chromatid loss contributed equally to chromosome malsegregation in the chl4 mutant. A genomic clone of CHL4 was isolated by complementation of the chl4-1 mutation and was physically mapped to the right arm of chromosome IV near the SUP2 gene. Nucleotide sequence analysis of CHL4 clone revealed a 1.4-kb open reading frame coding for a 53-kD predicted protein which does not have homology to published proteins. A strain containing a null allele of CHL4 is viable under standard growth conditions but has a temperature-sensitive phenotype (conditional lethality at 36 degrees). We suggest that the CHL4 gene is required for kinetochore function in the yeast Saccharomyces cerevisiae.

  9. Kinesin 5B (KIF5B is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.

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    Dawit Kidane

    Full Text Available The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD and failure in extrusion of the first polar body (PBE. In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  10. Kinesin 5B (KIF5B) is required for progression through female meiosis and proper chromosomal segregation in mitotic cells.

    Science.gov (United States)

    Kidane, Dawit; Sakkas, Denny; Nottoli, Timothy; McGrath, James; Sweasy, Joann B

    2013-01-01

    The fidelity of chromosomal segregation during cell division is important to maintain chromosomal stability in order to prevent cancer and birth defects. Although several spindle-associated molecular motors have been shown to be essential for cell division, only a few chromosome arm-associated motors have been described. Here, we investigated the role of Kinesin 5b (Kif5b) during female mouse meiotic cell development and mitotic cell division. RNA interference (RNAi)-mediated silencing of Kif5b in mouse oocytes induced significant delay in germinal vesicle breakdown (GVBD) and failure in extrusion of the first polar body (PBE). In mitotic cells, knockdown of Kif5b leads to centrosome amplification and a chromosomal segregation defect. These data suggest that KIF5B is critical in suppressing chromosomal instability at the early stages of female meiotic cell development and mitotic cell division.

  11. Spindle formation, chromosome segregation and the spindle checkpoint in mammalian oocytes and susceptibility to meiotic error.

    Science.gov (United States)

    Vogt, E; Kirsch-Volders, M; Parry, J; Eichenlaub-Ritter, U

    2008-03-12

    The spindle assembly checkpoint (SAC) monitors attachment to microtubules and tension on chromosomes in mitosis and meiosis. It represents a surveillance mechanism that halts cells in M-phase in the presence of unattached chromosomes, associated with accumulation of checkpoint components, in particular, Mad2, at the kinetochores. A complex between the anaphase promoting factor/cylosome (APC/C), its accessory protein Cdc20 and proteins of the SAC renders APC/C inactive, usually until all chromosomes are properly assembled at the spindle equator (chromosome congression) and under tension from spindle fibres. Upon release from the SAC the APC/C can target proteins like cyclin B and securin for degradation by the proteasome. Securin degradation causes activation of separase proteolytic enzyme, and in mitosis cleavage of cohesin proteins at the centromeres and arms of sister chromatids. In meiosis I only the cohesin proteins at the sister chromatid arms are cleaved. This requires meiosis specific components and tight regulation by kinase and phosphatase activities. There is no S-phase between meiotic divisions. Second meiosis resembles mitosis. Mammalian oocytes arrest constitutively at metaphase II in presence of aligned chromosomes, which is due to the activity of the cytostatic factor (CSF). The SAC has been identified in spermatogenesis and oogenesis, but gender-differences may contribute to sex-specific differential responses to aneugens. The age-related reduction in expression of components of the SAC in mammalian oocytes may act synergistically with spindle and other cell organelles' dysfunction, and a partial loss of cohesion between sister chromatids to predispose oocytes to errors in chromosome segregation. This might affect dose-response to aneugens. In view of the tendency to have children at advanced maternal ages it appears relevant to pursue studies on consequences of ageing on the susceptibility of human oocytes to the induction of meiotic error by

  12. Chromosome segregation and organization are targets of 5'-Fluorouracil in eukaryotic cells.

    Science.gov (United States)

    Mojardín, Laura; Botet, Javier; Moreno, Sergio; Salas, Margarita

    2015-01-01

    The antimetabolite 5'-Fluorouracil (5FU) is an analog of uracil commonly employed as a chemotherapeutic agent in the treatment of a range of cancers including colorectal tumors. To assess the cellular effects of 5FU, we performed a genome-wide screening of the haploid deletion library of the eukaryotic model Schizosaccharomyces pombe. Our analysis validated previously characterized drug targets including RNA metabolism, but it also revealed unexpected mechanisms of action associated with chromosome segregation and organization (post-translational histone modification, histone exchange, heterochromatin). Further analysis showed that 5FU affects the heterochromatin structure (decreased levels of histone H3 lysine 9 methylation) and silencing (down-regulation of heterochromatic dg/dh transcripts). To our knowledge, this is the first time that defects in heterochromatin have been correlated with increased cytotoxicity to an anticancer drug. Moreover, the segregation of chromosomes, a process that requires an intact heterochromatin at centromeres, was impaired after drug exposure. These defects could be related to the induction of genes involved in chromatid cohesion and kinetochore assembly. Interestingly, we also observed that thiabendazole, a microtubule-destabilizing agent, synergistically enhanced the cytotoxic effects of 5FU. These findings point to new targets and drug combinations that could potentiate the effectiveness of 5FU-based treatments.

  13. Specific and non-specific interactions of ParB with DNA: implications for chromosome segregation.

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    Taylor, James A; Pastrana, Cesar L; Butterer, Annika; Pernstich, Christian; Gwynn, Emma J; Sobott, Frank; Moreno-Herrero, Fernando; Dillingham, Mark S

    2015-01-01

    The segregation of many bacterial chromosomes is dependent on the interactions of ParB proteins with centromere-like DNA sequences called parS that are located close to the origin of replication. In this work, we have investigated the binding of Bacillus subtilis ParB to DNA in vitro using a variety of biochemical and biophysical techniques. We observe tight and specific binding of a ParB homodimer to the parS sequence. Binding of ParB to non-specific DNA is more complex and displays apparent positive co-operativity that is associated with the formation of larger, poorly defined, nucleoprotein complexes. Experiments with magnetic tweezers demonstrate that non-specific binding leads to DNA condensation that is reversible by protein unbinding or force. The condensed DNA structure is not well ordered and we infer that it is formed by many looping interactions between neighbouring DNA segments. Consistent with this view, ParB is also able to stabilize writhe in single supercoiled DNA molecules and to bridge segments from two different DNA molecules in trans. The experiments provide no evidence for the promotion of non-specific DNA binding and/or condensation events by the presence of parS sequences. The implications of these observations for chromosome segregation are discussed.

  14. Long G2 accumulates recombination intermediates and disturbs chromosome segregation at dysfunction telomere in Schizosaccharomyces pombe

    Energy Technology Data Exchange (ETDEWEB)

    Habib, Ahmed G.K.; Masuda, Kenta; Yukawa, Masashi; Tsuchiya, Eiko [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530 (Japan); Ueno, Masaru, E-mail: scmueno@hiroshima-u.ac.jp [Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530 (Japan); Research Center for the Mathematics on Chromatin Live Dynamics, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8530 (Japan)

    2015-08-14

    Protection of telomere (Pot1) is a single-stranded telomere binding protein which is essential for chromosome ends protection. Fission yeast Rqh1 is a member of RecQ helicases family which has essential roles in the maintenance of genomic stability and regulation of homologous recombination. Double mutant between fission yeast pot1Δ and rqh1 helicase dead (rqh1-hd) maintains telomere by homologous recombination. In pot1Δ rqh1-hd double mutant, recombination intermediates accumulate near telomere which disturb chromosome segregation and make cells sensitive to microtubule inhibitors thiabendazole (TBZ). Deletion of chk1{sup +} or mutation of its kinase domain shortens the G2 of pot1Δ rqh1-hd double mutant and suppresses both the accumulation of recombination intermediates and the TBZ sensitivity of that double mutant. In this study, we asked whether the long G2 is the reason for the TBZ sensitivity of pot1Δ rqh1-hd double mutant. We found that shortening the G2 of pot1Δ rqh1-hd double mutant by additional mutations of wee1 and mik1 or gain of function mutation of Cdc2 suppresses both the accumulation of recombination intermediates and the TBZ sensitivity of pot1Δ rqh1-hd double mutant. Our results suggest that long G2 of pot1Δ rqh1-hd double mutant may allow time for the accumulation of recombination intermediates which disturb chromosome segregation and make cells sensitive to TBZ. - Ηighlights: • We show link between long G2 and accumulation of toxic recombination intermediates. • Accumulation of recombination intermediates at telomere results in TBZ sensitivity. • Activation of DNA damage checkpoint worsens cells' viability in presence of TBZ.

  15. The bacterial chromosome segregation protein Spo0J spreads along DNA from parS nucleation sites.

    Science.gov (United States)

    Murray, Heath; Ferreira, Henrique; Errington, Jeff

    2006-09-01

    Regulation of chromosome inheritance is essential to ensure proper transmission of genetic information. To accomplish accurate genome segregation, cells organize their chromosomes and actively separate them prior to cytokinesis. In Bacillus subtilis the Spo0J protein is required for accurate chromosome segregation and it regulates the developmental switch from vegetative growth to sporulation. Spo0J is a DNA-binding protein that recognizes at least eight identified parS sites located near the origin of replication. As judged by fluorescence microscopy, Spo0J forms discrete foci associated with the oriC region of the chromosome throughout the cell cycle. In an attempt to determine the mechanisms utilized by Spo0J to facilitate productive chromosome segregation, we have investigated the DNA binding activity of Spo0J. In vivo we find Spo0J associates with several kilobases of DNA flanking its specific binding sites (parS) through a parS-dependent nucleation event that promotes lateral spreading of Spo0J along the chromosome. Using purified components we find that Spo0J has the ability to coat non-specific DNA substrates. These 'Spo0J domains' provide large structures near oriC that could potentially demark, organize or localize the origin region of the chromosome.

  16. Chromosome replication and segregation govern the biogenesis and inheritance of inorganic polyphosphate granules.

    Science.gov (United States)

    Henry, Jonathan T; Crosson, Sean

    2013-10-01

    Prokaryotes and eukaryotes synthesize long chains of orthophosphate, known as polyphosphate (polyP), which form dense granules within the cell. PolyP regulates myriad cellular functions and is often localized to specific subcellular addresses through mechanisms that remain undefined. In this study, we present a molecular-level analysis of polyP subcellular localization in the model bacterium Caulobacter crescentus. We demonstrate that biogenesis and localization of polyP is controlled as a function of the cell cycle, which ensures regular partitioning of granules between mother and daughter. The enzyme polyphosphate kinase 1 (Ppk1) is required for granule production, colocalizes with granules, and dynamically localizes to the sites of new granule synthesis in nascent daughter cells. Localization of Ppk1 within the cell requires an intact catalytic active site and a short, positively charged tail at the C-terminus of the protein. The processes of chromosome replication and segregation govern both the number and position of Ppk1/polyP complexes within the cell. We propose a multistep model in which the chromosome establishes sites of polyP coalescence, which recruit Ppk1 to promote the in situ synthesis of large granules. These findings underscore the importance of both chromosome dynamics and discrete protein localization as organizing factors in bacterial cell biology.

  17. Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation.

    Science.gov (United States)

    Lim, Hoong Chuin; Surovtsev, Ivan Vladimirovich; Beltran, Bruno Gabriel; Huang, Fang; Bewersdorf, Jörg; Jacobs-Wagner, Christine

    2014-05-23

    The widely conserved ParABS system plays a major role in bacterial chromosome segregation. How the components of this system work together to generate translocation force and directional motion remains uncertain. Here, we combine biochemical approaches, quantitative imaging and mathematical modeling to examine the mechanism by which ParA drives the translocation of the ParB/parS partition complex in Caulobacter crescentus. Our experiments, together with simulations grounded on experimentally-determined biochemical and cellular parameters, suggest a novel 'DNA-relay' mechanism in which the chromosome plays a mechanical function. In this model, DNA-bound ParA-ATP dimers serve as transient tethers that harness the elastic dynamics of the chromosome to relay the partition complex from one DNA region to another across a ParA-ATP dimer gradient. Since ParA-like proteins are implicated in the partitioning of various cytoplasmic cargos, the conservation of their DNA-binding activity suggests that the DNA-relay mechanism may be a general form of intracellular transport in bacteria.DOI: http://dx.doi.org/10.7554/eLife.02758.001.

  18. Cohesins: chromatin architects in chromosome segregation, control of gene expression and much more.

    Science.gov (United States)

    Barbero, José L

    2009-07-01

    Cells have evolved to develop molecules and control mechanisms that guarantee correct chromosome segregation and ensure the proper distribution of genetic material to daughter cells. In this sense, the establishment, maintenance, and removal of sister chromatid cohesion is one of the most fascinating and dangerous processes in the life of a cell because errors in the control of these processes frequently lead to cell death or aneuploidy. The main protagonist in this mechanism is a four-protein complex denominated the cohesin complex. In the last 10 years, we have improved our understanding of the key players in the regulation of sister chromatid cohesion during cell division in mitosis and meiosis. The last 2 years have seen an increase in evidence showing that cohesins have important functions in non-dividing cells, revealing new, unexplored roles for these proteins in the control of gene expression, development, and other essential cell functions in mammals.

  19. A multidomain hub anchors the chromosome segregation and chemotactic machinery to the bacterial pole.

    Science.gov (United States)

    Yamaichi, Yoshiharu; Bruckner, Raphael; Ringgaard, Simon; Möll, Andrea; Cameron, D Ewen; Briegel, Ariane; Jensen, Grant J; Davis, Brigid M; Waldor, Matthew K

    2012-10-15

    The cell poles constitute key subcellular domains that are often critical for motility, chemotaxis, and chromosome segregation in rod-shaped bacteria. However, in nearly all rods, the processes that underlie the formation, recognition, and perpetuation of the polar domains are largely unknown. Here, in Vibrio cholerae, we identified HubP (hub of the pole), a polar transmembrane protein conserved in all vibrios, that anchors three ParA-like ATPases to the cell poles and, through them, controls polar localization of the chromosome origin, the chemotactic machinery, and the flagellum. In the absence of HubP, oriCI is not targeted to the cell poles, chemotaxis is impaired, and a small but increased fraction of cells produces multiple, rather than single, flagella. Distinct cytoplasmic domains within HubP are required for polar targeting of the three ATPases, while a periplasmic portion of HubP is required for its localization. HubP partially relocalizes from the poles to the mid-cell prior to cell division, thereby enabling perpetuation of the polar domain in future daughter cells. Thus, a single polar hub is instrumental for establishing polar identity and organization.

  20. Phospho-Bcl-xL(Ser62) influences spindle assembly and chromosome segregation during mitosis.

    Science.gov (United States)

    Wang, Jianfang; Beauchemin, Myriam; Bertrand, Richard

    2014-01-01

    Functional analysis of a series of phosphorylation mutants reveals that Bcl-xL(Ser62Ala) influences cell entry into anaphase and mitotic exit in taxol-exposed cells compared with cells expressing wild-type Bcl-xL or a series of other phosphorylation mutants, an effect that appears to be independent of its anti-apoptotic activity. During normal mitosis progression, Bcl-xL(Ser62) is strongly phosphorylated by PLK1 and MAPK14/SAPKp38α at the prometaphase, metaphase, and the anaphase boundaries, while it is de-phosphorylated at telophase and cytokinesis. Phospho-Bcl-xL(Ser62) localizes in centrosomes with γ-tubulin and in the mitotic cytosol with some spindle-assembly checkpoint signaling components, including PLK1, BubR1, and Mad2. In taxol- and nocodazole-exposed cells, phospho-Bcl-xL(Ser62) also binds to Cdc20- Mad2-, BubR1-, and Bub3-bound complexes, while Bcl-xL(Ser62Ala) does not. Silencing Bcl-xL expression and expressing the phosphorylation mutant Bcl-xL(Ser62Ala) lead to an increased number of cells harboring mitotic spindle defects including multipolar spindle, chromosome lagging and bridging, aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h. Together, the data indicate that during mitosis, Bcl-xL(Ser62) phosphorylation impacts on spindle assembly and chromosome segregation, influencing chromosome stability. Observations of mitotic cells harboring aneuploidy with micro-, bi-, or multi-nucleated cells, and cells that fail to resolve undergo mitosis within 6 h were also made with cells expressing the phosphorylation mutant Bcl-xL(Ser49Ala) and dual mutant Bcl-xL(Ser49/62Ala).

  1. A defined terminal region of the E. coli chromosome shows late segregation and high FtsK activity.

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    Marie Deghorain

    Full Text Available BACKGROUND: The FtsK DNA-translocase controls the last steps of chromosome segregation in E. coli. It translocates sister chromosomes using the KOPS DNA motifs to orient its activity, and controls the resolution of dimeric forms of sister chromosomes by XerCD-mediated recombination at the dif site and their decatenation by TopoIV. METHODOLOGY: We have used XerCD/dif recombination as a genetic trap to probe the interaction of FtsK with loci located in different regions of the chromosome. This assay revealed that the activity of FtsK is restricted to a ∼400 kb terminal region of the chromosome around the natural position of the dif site. Preferential interaction with this region required the tethering of FtsK to the division septum via its N-terminal domain as well as its translocation activity. However, the KOPS-recognition activity of FtsK was not required. Displacement of replication termination outside the FtsK high activity region had no effect on FtsK activity and deletion of a part of this region was not compensated by its extension to neighbouring regions. By observing the fate of fluorescent-tagged loci of the ter region, we found that segregation of the FtsK high activity region is delayed compared to that of its adjacent regions. SIGNIFICANCE: Our results show that a restricted terminal region of the chromosome is specifically dedicated to the last steps of chromosome segregation and to their coupling with cell division by FtsK.

  2. Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

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    Harris William A

    2009-07-01

    Full Text Available Abstract Background The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described. Results Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in cap-g mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes. Conclusion Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.

  3. Conjugal plasmid transfer in Streptomyces resembles bacterial chromosome segregation by FtsK/SpoIIIE.

    Science.gov (United States)

    Vogelmann, Jutta; Ammelburg, Moritz; Finger, Constanze; Guezguez, Jamil; Linke, Dirk; Flötenmeyer, Matthias; Stierhof, York-Dieter; Wohlleben, Wolfgang; Muth, Günther

    2011-06-01

    Conjugation is a major route of horizontal gene transfer, the driving force in the evolution of bacterial genomes. Antibiotic producing soil bacteria of the genus Streptomyces transfer DNA in a unique process involving a single plasmid-encoded protein TraB and a double-stranded DNA molecule. However, the molecular function of TraB in directing DNA transfer from a donor into a recipient cell is unknown. Here, we show that TraB constitutes a novel conjugation system that is clearly distinguished from DNA transfer by a type IV secretion system. We demonstrate that TraB specifically recognizes and binds to repeated 8 bp motifs on the conjugative plasmid. The specific DNA recognition is mediated by helix α3 of the C-terminal winged-helix-turn-helix domain of TraB. We show that TraB assembles to a hexameric ring structure with a central ∼3.1 nm channel and forms pores in lipid bilayers. Structure, sequence similarity and DNA binding characteristics of TraB indicate that TraB is derived from an FtsK-like ancestor protein, suggesting that Streptomyces adapted the FtsK/SpoIIIE chromosome segregation system to transfer DNA between two distinct Streptomyces cells.

  4. Segregation of chromosome arms in growing and non-growing Escherichia coli cells

    DEFF Research Database (Denmark)

    Woldringh, Conrad L.; Hansen, Flemming G.; Vischer, Norbert O. E.;

    2015-01-01

    In slow-growing Escherichia coli cells the chromosome is organized with its left (L) and right (R) arms lying separated in opposite halves of the nucleoid and with the origin (0) in-between, giving the pattern L-O-R. During replication one of the arms has to pass the other to obtain the same...... organization in the daughter cells: L-O-R L-O-R. To determine the movement of arms during segregation six strains were constructed carrying three colored loci: the left and right arms were labeled with red and cyan fluorescent-proteins, respectively, on loci symmetrically positioned at different distances from...... that the movement of arms is not a growth-sustained process, but may result from DNA synthesis itself. The distances between loci on different arms (LR-distances) and between duplicated loci (LL- or RR-distances) as a function of their distance from the origin, indicate that in slow-growing cells DNA is organized...

  5. Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast.

    Directory of Open Access Journals (Sweden)

    Gloria Palou

    2015-09-01

    Full Text Available A surveillance mechanism, the S phase checkpoint, blocks progression into mitosis in response to DNA damage and replication stress. Segregation of damaged or incompletely replicated chromosomes results in genomic instability. In humans, the S phase checkpoint has been shown to constitute an anti-cancer barrier. Inhibition of mitotic cyclin dependent kinase (M-CDK activity by Wee1 kinases is critical to block mitosis in some organisms. However, such mechanism is dispensable in the response to genotoxic stress in the model eukaryotic organism Saccharomyces cerevisiae. We show here that the Wee1 ortholog Swe1 does indeed inhibit M-CDK activity and chromosome segregation in response to genotoxic insults. Swe1 dispensability in budding yeast is the result of a redundant control of M-CDK activity by the checkpoint kinase Rad53. In addition, our results indicate that Swe1 is an effector of the checkpoint central kinase Mec1. When checkpoint control on M-CDK and on Pds1/securin stabilization are abrogated, cells undergo aberrant chromosome segregation.

  6. Segregation of chromosome arms in growing and non-growing Escherichia coli cells

    Directory of Open Access Journals (Sweden)

    Conrad L. Woldringh

    2015-05-01

    Full Text Available In slow-growing Escherichia coli cells the chromosome is organized with its left (L and right (R arms lying separated in opposite halves of the nucleoid and with the origin (O in-between, giving the pattern L-O-R. During replication one of the arms has to pass the other to obtain the same organization in the daughter cells: L-O-R L-O-R. To determine the movement of arms during segregation six strains were constructed carrying three coloured loci: the left and right arms were labeled with red and cyan fluorescent-proteins, respectively, on loci symmetrically positioned at different distances from the central origin, which was labeled with green-fluorescent protein. In non-replicating cells with the predominant spot pattern L-O-R, initiation of replication first resulted in a L-O-O-R pattern, soon changing to O-L-R-O. After replication of the arms the predominant spot patterns were, L-O-R L-O-R, O-R-L R-O-L or O-L-R L-O-R indicating that one or both arms passed an origin and the other arm. To study the driving force for these movements cell growth was inhibited with rifampicin allowing run-off DNA synthesis. Similar spot patterns were obtained in growing and non-growing cells, indicating that the movement of arms is not a growth-sustained process, but may result from DNA synthesis itself. The distances between loci on different arms (LR-distances and between duplicated loci (LL- or RR-distances as a function of their distance from the origin, indicate that in slow-growing cells DNA is organized according to the so-called sausage model and not accordingto the doughnut model.

  7. Sex without sex chromosomes: genetic architecture of multiple loci independently segregating to determine sex ratios in the copepod Tigriopus californicus.

    Science.gov (United States)

    Alexander, H J; Richardson, J M L; Edmands, S; Anholt, B R

    2015-12-01

    Sex-determining systems are remarkably diverse and may evolve rapidly. Polygenic sex-determination systems are predicted to be transient and evolutionarily unstable, yet examples have been reported across a range of taxa. Here, we provide the first direct evidence of polygenic sex determination in Tigriopus californicus, a harpacticoid copepod with no heteromorphic sex chromosomes. Using genetically distinct inbred lines selected for male- and female-biased clutches, we generated a genetic map with 39 SNPs across 12 chromosomes. Quantitative trait locus mapping of sex ratio phenotype (the proportion of male offspring produced by an F2 female) in four F2 families revealed six independently segregating quantitative trait loci on five separate chromosomes, explaining 19% of the variation in sex ratios. The sex ratio phenotype varied among loci across chromosomes in both direction and magnitude, with the strongest phenotypic effects on chromosome 10 moderated to some degree by loci on four other chromosomes. For a given locus, sex ratio phenotype varied in magnitude for individuals derived from different dam lines. These data, together with the environmental factors known to contribute to sex determination, characterize the underlying complexity and potential lability of sex determination, and confirm the polygenic architecture of sex determination in T. californicus.

  8. X chromosome-linked and mitochondrial gene control of Leber hereditary optic neuropathy: Evidence from segregation analysis for dependence on X chromosome inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Xiangdong Bu; Rotter, J.I. (Cedars-Sinai Medical Center, Los Angeles, CA (United States) Univ. of California, Los Angeles (United States))

    1991-09-15

    Leber hereditary optic neuropathy (LHON) has been shown to involve mutation(s) of mitochondrial DNA, yet there remain several confusing aspects of its inheritance not explained by mitochondrial inheritance alone, including male predominance, reduced penetrance, and a later age of onset in females. By extending segregation analysis methods to disorders that involve both a mitochondrial and a nuclear gene locus, the authors show that the available pedigree data for LHON are most consistent with a two-locus disorder, with one responsible gene being mitochondrial and the other nuclear and X chromosome-linked. Furthermore, they have been able to extend the two-locus analytic method and demonstrate that a proportion of affected females are likely heterozygous at the X chromosome-linked locus and are affected due to unfortunate X chromosome inactivation, thus providing an explanation for the later age of onset in females. The estimated penetrance for a heterozygous female is 0.11{plus minus}0.02. The calculated frequency of the X chromosome-linked gene for LHON is 0.l08. Among affected females, 60% are expected to be heterozygous, and the remainder are expected to be homozygous at the responsible X chromosome-linked locus.

  9. Why is chromosome segregation error in oocytes increased with maternal aging?

    Science.gov (United States)

    Wang, Zhen-Bo; Schatten, Heide; Sun, Qing-Yuan

    2011-10-01

    It is well documented that female fertility is decreased with advanced maternal age due to chromosome abnormality in oocytes. Increased chromosome missegregation is mainly caused by centromeric cohesion reduction. Other factors such as weakened homologous recombination, improper spindle organization, spindle assembly checkpoint (SAC) malfunction, chromatin epigenetic changes, and extra-oocyte factors may also cause chromosome errors.

  10. The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation.

    Science.gov (United States)

    Claycomb, Julie M; Batista, Pedro J; Pang, Ka Ming; Gu, Weifeng; Vasale, Jessica J; van Wolfswinkel, Josien C; Chaves, Daniel A; Shirayama, Masaki; Mitani, Shohei; Ketting, René F; Conte, Darryl; Mello, Craig C

    2009-10-02

    RNAi-related pathways regulate diverse processes, from developmental timing to transposon silencing. Here, we show that in C. elegans the Argonaute CSR-1, the RNA-dependent RNA polymerase EGO-1, the Dicer-related helicase DRH-3, and the Tudor-domain protein EKL-1 localize to chromosomes and are required for proper chromosome segregation. In the absence of these factors chromosomes fail to align at the metaphase plate and kinetochores do not orient to opposing spindle poles. Surprisingly, the CSR-1-interacting small RNAs (22G-RNAs) are antisense to thousands of germline-expressed protein-coding genes. Nematodes assemble holocentric chromosomes in which continuous kinetochores must span the expressed domains of the genome. We show that CSR-1 interacts with chromatin at target loci but does not downregulate target mRNA or protein levels. Instead, our findings support a model in which CSR-1 complexes target protein-coding domains to promote their proper organization within the holocentric chromosomes of C. elegans.

  11. Rejuvenation of meiotic cohesion in oocytes during prophase I is required for chiasma maintenance and accurate chromosome segregation.

    Science.gov (United States)

    Weng, Katherine A; Jeffreys, Charlotte A; Bickel, Sharon E

    2014-09-01

    Chromosome segregation errors in human oocytes are the leading cause of birth defects, and the risk of aneuploid pregnancy increases dramatically as women age. Accurate segregation demands that sister chromatid cohesion remain intact for decades in human oocytes, and gradual loss of the original cohesive linkages established in fetal oocytes is proposed to be a major cause of age-dependent segregation errors. Here we demonstrate that maintenance of meiotic cohesion in Drosophila oocytes during prophase I requires an active rejuvenation program, and provide mechanistic insight into the molecular events that underlie rejuvenation. Gal4/UAS inducible knockdown of the cohesion establishment factor Eco after meiotic S phase, but before oocyte maturation, causes premature loss of meiotic cohesion, resulting in destabilization of chiasmata and subsequent missegregation of recombinant homologs. Reduction of individual cohesin subunits or the cohesin loader Nipped B during prophase I leads to similar defects. These data indicate that loading of newly synthesized replacement cohesin rings by Nipped B and establishment of new cohesive linkages by the acetyltransferase Eco must occur during prophase I to maintain cohesion in oocytes. Moreover, we show that rejuvenation of meiotic cohesion does not depend on the programmed induction of meiotic double strand breaks that occurs during early prophase I, and is therefore mechanistically distinct from the DNA damage cohesion re-establishment pathway identified in G2 vegetative yeast cells. Our work provides the first evidence that new cohesive linkages are established in Drosophila oocytes after meiotic S phase, and that these are required for accurate chromosome segregation. If such a pathway also operates in human oocytes, meiotic cohesion defects may become pronounced in a woman's thirties, not because the original cohesive linkages finally give out, but because the rejuvenation program can no longer supply new cohesive linkages

  12. Chromosome segregation regulation in human zygotes : Altered mitotic histone phosphorylation dynamics underlying centromeric targeting of the chromosomal passenger complex

    NARCIS (Netherlands)

    Van De Werken, C.; Avo Santos, M.; Laven, J. S E; Eleveld, C.; Fauser, B. C J M; Lens, S. M A; Baart, E. B.

    2015-01-01

    STUDY QUESTION Are the kinase feedback loops that regulate activation and centromeric targeting of the chromosomal passenger complex (CPC), functional during mitosis in human embryos? SUMMARY ANSWER Investigation of the regulatory kinase pathways involved in centromeric CPC targeting revealed normal

  13. SpoIIIE and a novel type of DNA translocase, SftA, couple chromosome segregation with cell division in Bacillus subtilis.

    Science.gov (United States)

    Kaimer, Christine; González-Pastor, José Eduardo; Graumann, Peter L

    2009-11-01

    Cell division must only occur once daughter chromosomes have been fully separated. However, the initiating event of bacterial cell division, assembly of the FtsZ ring, occurs while chromosome segregation is still ongoing. We show that a two-step DNA translocase system exists in Bacillus subtilis that couples chromosome segregation and cell division. The membrane-bound DNA translocase SpoIIIE assembled very late at the division septum, and only upon entrapment of DNA, while its orthologue, SftA (YtpST), assembled at each septum in B. subtilis soon after FtsZ. Lack of SftA resulted in a moderate segregation defect at a late stage in the cell cycle. Like the loss of SpoIIIE, the absence of SftA was deleterious for the cells during conditions of defective chromosome segregation, or after induction of DNA damage. Lack of both proteins exacerbated all phenotypes. SftA forms soluble hexamers in solution, binds to DNA and has DNA-dependent ATPase activity, which is essential for its function in vivo. Our data suggest that SftA aids in moving DNA away from the closing septum, while SpoIIIE translocates septum-entrapped DNA only when septum closure precedes complete segregation of chromosomes.

  14. Split hand/foot malformation genetics supports the chromosome 7 copy segregation mechanism for human limb development

    Science.gov (United States)

    Klar, Amar J. S.

    2016-01-01

    Genetic aberrations of several unlinked loci cause human congenital split hand/foot malformation (SHFM) development. Mutations of the DLX5 (distal-less) transcription factor-encoding gene in chromosome 7 cause SHFM through haploinsufficiency, but the vast majority of cases result from heterozygous chromosomal aberrations of the region without mutating the DLX5 gene. To resolve this paradox, we invoke a chromosomal epigenetic mechanism for limb development. It is composed of a monochromatid gene expression phenomenon that we discovered in two fission yeasts with the selective chromosome copy segregation phenomenon that we discovered in mouse cells. Accordingly, one daughter cell inherits both expressed DLX5 copies while the other daughter inherits both epigenetically silenced ones from a single deterministic cell of the developing limb. Thus, differentiated daughter cells after further proliferation will correspondingly produce proximal/distal-limb tissues. Published results of a Chr. 7 translocation with a centromere-proximal breakpoint situated over 41 million bases away from the DLX locus, centromeric and DLX5-region inversions have satisfied key genetic and developmental biology predictions of the mechanism. Further genetic tests of the mechanism are proposed. We propose that the DNA double helical structure itself causes the development of sister cells' gene regulation asymmetry. We also argue against the conventionally invoked morphogen model of development. This article is part of the themed issue ‘Provocative questions in left–right asymmetry’. PMID:27821526

  15. Dynamic interplay of ParA with the polarity protein, Scy, coordinates the growth with chromosome segregation in Streptomyces coelicolor.

    Science.gov (United States)

    Ditkowski, Bartosz; Holmes, Neil; Rydzak, Joanna; Donczew, Magdalena; Bezulska, Martyna; Ginda, Katarzyna; Kedzierski, Pawel; Zakrzewska-Czerwińska, Jolanta; Kelemen, Gabriella H; Jakimowicz, Dagmara

    2013-03-27

    Prior to bacterial cell division, the ATP-dependent polymerization of the cytoskeletal protein, ParA, positions the newly replicated origin-proximal region of the chromosome by interacting with ParB complexes assembled on parS sites located close to the origin. During the formation of unigenomic spores from multi-genomic aerial hyphae compartments of Streptomyces coelicolor, ParA is developmentally triggered to form filaments along the hyphae; this promotes the accurate and synchronized segregation of tens of chromosomes into prespore compartments. Here, we show that in addition to being a segregation protein, ParA also interacts with the polarity protein, Scy, which is a component of the tip-organizing centre that controls tip growth. Scy recruits ParA to the hyphal tips and regulates ParA polymerization. These results are supported by the phenotype of a strain with a mutant form of ParA that uncouples ParA polymerization from Scy. We suggest that the ParA-Scy interaction coordinates the transition from hyphal elongation to sporulation.

  16. The actinobacterial signature protein ParJ (SCO1662) regulates ParA polymerization and affects chromosome segregation and cell division during Streptomyces sporulation.

    Science.gov (United States)

    Ditkowski, Bartosz; Troć, Paulina; Ginda, Katarzyna; Donczew, Magdalena; Chater, Keith F; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2010-12-01

    Bacterial chromosome segregation usually involves cytoskeletal ParA proteins, ATPases which can form dynamic filaments. In aerial hyphae of the mycelial bacterium Streptomyces coelicolor, ParA filaments extend over tens of microns and are responsible for segregation of dozens of chromosomes. We have identified a novel interaction partner of S. coelicolor ParA, ParJ. ParJ negatively regulates ParA polymerization in vitro and is important for efficient chromosome segregation in sporulating aerial hyphae. ParJ-EGFP formed foci along aerial hyphae even in the absence of ParA. ParJ, which is encoded by sco1662, turned out to be one of the five actinobacterial signature proteins, and another of the five is a ParJ paralogue. We hypothesize that polar growth, which is characteristic not only of streptomycetes, but even of simple Actinobacteria, may be interlinked with ParA polymer assembly and its specific regulation by ParJ.

  17. Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes.

    Science.gov (United States)

    Derive, Nicolas; Landmann, Cedric; Montembault, Emilie; Claverie, Marie-Charlotte; Pierre-Elies, Priscillia; Goutte-Gattat, Damien; Founounou, Nabila; McCusker, Derek; Royou, Anne

    2015-11-09

    The presence of DNA double-strand breaks during mitosis is particularly challenging for the cell, as it produces broken chromosomes lacking a centromere. This situation can cause genomic instability resulting from improper segregation of the broken fragments into daughter cells. We recently uncovered a process by which broken chromosomes are faithfully transmitted via the BubR1-dependent tethering of the two broken chromosome ends. However, the mechanisms underlying BubR1 recruitment and function on broken chromosomes were largely unknown. We show that BubR1 requires interaction with Bub3 to localize on the broken chromosome fragments and to mediate their proper segregation. We also find that Cdc20, a cofactor of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), accumulates on DNA breaks in a BubR1 KEN box-dependent manner. A biosensor for APC/C activity demonstrates a BubR1-dependent local inhibition of APC/C around the segregating broken chromosome. We therefore propose that the Bub3-BubR1 complex on broken DNA inhibits the APC/C locally via the sequestration of Cdc20, thus promoting proper transmission of broken chromosomes.

  18. Comprehensive meiotic segregation analysis of a 4-breakpoint t(1;3;6) complex chromosome rearrangement using single sperm array comparative genomic hybridization and FISH.

    Science.gov (United States)

    Hornak, Miroslav; Vozdova, Miluse; Musilova, Petra; Prinosilova, Petra; Oracova, Eva; Linkova, Vlasta; Vesela, Katerina; Rubes, Jiri

    2014-10-01

    Complex chromosomal rearrangements (CCR) represent rare structural chromosome abnormalities frequently associated with infertility. In this study, meiotic segregation in spermatozoa of an infertile normospermic carrier of a 4-breakpoint t(1;3;6) CCR was analysed. A newly developed array comparative genomic hybridization protocol was used, and all chromosomes in 50 single sperm cells were simultaneously examined. Three-colour FISH was used to analyse chromosome segregation in 1557 other single sperm cells. It was also used to measure an interchromosomal effect; sperm chromatin structure assay was used to measure chromatin integrity. A high-frequency of unbalanced spermatozoa (84%) was observed, mostly arising from the 3:3 symmetrical segregation mode. Array comparative genomic hybridization was used to detect additional aneuploidies in two out of 50 spermatozoa (4%) in chromosomes not involved in the complex chromosome rearrangement. Significantly increased rates of diploidy and XY disomy were found in the CCR carrier compared with the control group (P < 0.001). Defective condensation of sperm chromatin was also found in 22.7% of spermatozoa by sperm chromatin structure assay. The results indicate that the infertility in the man with CCR and normal spermatozoa was caused by a production of chromosomally unbalanced, XY disomic and diploid spermatozoa and spermatozoa with defective chromatin condensation.

  19. The role of meiotic cohesin REC8 in chromosome segregation in {gamma} irradiation-induced endopolyploid tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Erenpreisa, Jekaterina [Latvian Biomedicine Research and Study Centre, Riga, LV-1067 (Latvia); Cragg, Mark S. [Tenovus Laboratory, Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton SO16 6YD (United Kingdom); Salmina, Kristine [Latvian Biomedicine Research and Study Centre, Riga, LV-1067 (Latvia); Hausmann, Michael [Kirchhoff Inst. fuer Physik, Univ. of Heidelberg, D-69120 Heidelberg (Germany); Scherthan, Harry, E-mail: scherth@web.de [Inst. fuer Radiobiologie der Bundeswehr in Verbindung mit der Univ. Ulm, D-80937 Munich (Germany); MPI for Molec. Genetics, 14195 Berlin (Germany)

    2009-09-10

    Escape from mitotic catastrophe and generation of endopolyploid tumour cells (ETCs) represents a potential survival strategy of tumour cells in response to genotoxic treatments. ETCs that resume the mitotic cell cycle have reduced ploidy and are often resistant to these treatments. In search for a mechanism for genome reduction, we previously observed that ETCs express meiotic proteins among which REC8 (a meiotic cohesin component) is of particular interest, since it favours reductional cell division in meiosis. In the present investigation, we induced endopolyploidy in p53-dysfunctional human tumour cell lines (Namalwa, WI-L2-NS, HeLa) by gamma irradiation, and analysed the sub-cellular localisation of REC8 in the resulting ETCs. We observed by RT-PCR and Western blot that REC8 is constitutively expressed in these tumour cells, along with SGOL1 and SGOL2, and that REC8 becomes modified after irradiation. REC8 localised to paired sister centromeres in ETCs, the former co-segregating to opposite poles. Furthermore, REC8 localised to the centrosome of interphase ETCs and to the astral poles in anaphase cells where it colocalised with the microtubule-associated protein NuMA. Altogether, our observations indicate that radiation-induced ETCs express features of meiotic cell divisions and that these may facilitate chromosome segregation and genome reduction.

  20. Coordination between chromosome replication, segregation, and cell division in Caulobacter crescentus

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    , and the completely replicated terminus regions stay associated with each other after chromosome replication is completed, disassociating very late in the cell cycle shortly before the final cell division event. Invagination of the cytoplasmic membrane occurs earlier than separation of the replicated terminus regions...... and formation of separate nucleoids, which results in trapping of a chromosome on either side of the cell division septum, indicating that there is not a nucleoid exclusion phenotype.......Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication...

  1. Bacterial chromosome segregation: structure and DNA binding of the Soj dimer — a conserved biological switch

    OpenAIRE

    Leonard, Thomas A.; Butler, P Jonathan; Löwe, Jan

    2005-01-01

    Soj and Spo0J of the Gram-negative hyperthermophile Thermus thermophilus belong to the conserved ParAB family of bacterial proteins implicated in plasmid and chromosome partitioning. Spo0J binds to DNA near the replication origin and localises at the poles following initiation of replication. Soj oscillates in the nucleoid region in an ATP- and Spo0J-dependent fashion. Here, we show that Soj undergoes ATP-dependent dimerisation in solution and forms nucleoprotein filaments with DNA. Crystal s...

  2. High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation.

    NARCIS (Netherlands)

    Jehee, F.S.; Krepischi-Santos, A.C.; Rocha, K.M.; Cavalcanti, D.P.; Kim, C.A.; Bertola, D.R.; Alonso, L.G.; D'Angelo, C.S.; Mazzeu, J.F.; Froyen, G.; Lugtenberg, D.; Vianna-Morgante, A.M.; Rosenberg, C.; Passos-Bueno, M.R.

    2008-01-01

    We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric

  3. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  4. Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

    Directory of Open Access Journals (Sweden)

    Grégory Baronian

    Full Text Available Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

  5. Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

    Science.gov (United States)

    Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

    2015-01-01

    Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

  6. PprA Protein Is Involved in Chromosome Segregation via Its Physical and Functional Interaction with DNA Gyrase in Irradiated Deinococcus radiodurans Bacteria.

    Science.gov (United States)

    Devigne, Alice; Guérin, Philippe; Lisboa, Johnny; Quevillon-Cheruel, Sophie; Armengaud, Jean; Sommer, Suzanne; Bouthier de la Tour, Claire; Servant, Pascale

    2016-01-01

    PprA, a radiation-induced Deinococcus-specific protein, was previously shown to be required for cell survival and accurate chromosome segregation after exposure to ionizing radiation. Here, we used an in vivo approach to determine, by shotgun proteomics, putative PprA partners coimmunoprecipitating with PprA when cells were exposed to gamma rays. Among them, we found the two subunits of DNA gyrase and, thus, chose to focus our work on characterizing the activities of the deinococcal DNA gyrase in the presence or absence of PprA. Loss of PprA rendered cells hypersensitive to novobiocin, an inhibitor of the B subunit of DNA gyrase. We showed that treatment of bacteria with novobiocin resulted in induction of the radiation desiccation response (RDR) regulon and in defects in chromosome segregation that were aggravated by the absence of PprA. In vitro, the deinococcal DNA gyrase, like other bacterial DNA gyrases, possesses DNA negative supercoiling and decatenation activities. These two activities are inhibited in vitro by novobiocin and nalidixic acid, whereas PprA specifically stimulates the decatenation activity of DNA gyrase. Together, these results suggest that PprA plays a major role in chromosome decatenation via its interaction with the deinococcal DNA gyrase when D. radiodurans cells are recovering from exposure to ionizing radiation. IMPORTANCE D. radiodurans is one of the most radiation-resistant organisms known. This bacterium is able to cope with high levels of DNA lesions generated by exposure to extreme doses of ionizing radiation and to reconstruct a functional genome from hundreds of radiation-induced chromosomal fragments. Here, we identified partners of PprA, a radiation-induced Deinococcus-specific protein, previously shown to be required for radioresistance. Our study leads to three main findings: (i) PprA interacts with DNA gyrase after irradiation, (ii) treatment of cells with novobiocin results in defects in chromosome segregation that are

  7. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells.

    Directory of Open Access Journals (Sweden)

    William T Silkworth

    Full Text Available Many cancer cells display a CIN (Chromosome Instability phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed gamma-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells.

  8. MreBCD-associated Cytoskeleton is Required for Proper Segregation of the Chromosomal Terminus during the Division Cycle of Escherichia Coli

    Institute of Scientific and Technical Information of China (English)

    Yu-Jia Huo; Ling Qiao; Xiao-Wei Zheng; Cheng Cui; Yuan-Fang Ma; Feng Lu

    2015-01-01

    Background:In prokaryotic organisms,the mechanism responsible for the accurate partition of newly replicated chromosomes into daughter cells is incompletely understood.Segregation of the replication terminus of the circular prokaryotic chromosome poses special problems that have not previously been addressed.The aim of this study was to investigate the roles of several protein components (MreB,MreC,and MreD) of the prokaryotic cytoskeleton for the faithful transmission of the chromosomal terminus into daughter cells.Methods:Strain LQ1 (mreB::cat),LQ2 (mreC::cat),and LQ3 (mreD::cat) were constructed using the Red recombination system.LQ11/pLAU53,LQ12/pLAU53,LQ13/pLAU53,LQ14/pLAU53,and LQ15/pLAU53 strains were generated by Pltransduction of (tetO)240-Gm and (lacO)240-Km cassettes from strains IL2 and IL29.Fluorescence microscopy was performed to observe localization pattern of fluorescently-labeled origin and terminus foci in wild-type and mutant cells.SOS induction was monitored as gfp fluorescence from PsulA-gfp in log phase cells grown in Luria-Bertani medium at 37℃ by measurement of emission at 525 nm with excitation at 470 nm in a microplate fluorescence reader.Results:Mutational deletion of the mreB,mreC,or mreD genes was associated with selective loss of the terminus region in approximately 40% of the cells within growing cultures.This was accompanied by significant induction of the SOS DNA damage response,suggesting that deletion of terminus sequences may have occurred by chromosomal cleavage,presumably caused by ingrowth of the division septum prior to segregation of the replicated terminal.Conclusions:These results imply a role for the MreBCD cytoskeleton in the resolution of the final products of terminus replication and/ or in the specific movement of newly replicated termini away from midcell prior to completion of septal ingrowth.This would identify a previously unrecognized stage in the overall process of chromosome segregation.

  9. Chromosome

    Science.gov (United States)

    Chromosomes are structures found in the center (nucleus) of cells that carry long pieces of DNA. DNA ... is the building block of the human body. Chromosomes also contain proteins that help DNA exist in ...

  10. Effects of age on segregation of the X and Y chromosomes in cultured lymphocytes from Chinese men.

    Science.gov (United States)

    Song, Yaxian; Chen, Qian; Zhang, Zhen; Hou, Heli; Zhang, Ding; Shi, Qinghua

    2009-08-01

    Chromosome malsegregation in binucleated lymphocytes is a useful endpoint to evaluate age effect on genetic stability. However, the investigations on chromosome malsegregation in binucleated lymphocytes from Chinese are scarce. In this study, peripheral blood lymphocytes were collected from 14 old (60-70 years) and 10 young (22-26 years) healthy Chinese men. To detect malsegregation of the sex chromosomes, multi-color fluorescence in situ hybridization (FISH) was performed on binucleated lymphocytes, cytokinesis-blocked by cytochalasin B at the first mitosis after phytohaemagglutinin stimulation. Compared with that in young men, a significant increase in frequencies of loss of chromosome X (9.2 +/- 3.2 per thousand vs. 1.1 +/- 0.9 per thousand, P men. Similarly, nondisjunction of chromosome X (16.5 +/- 3.4 per thousand vs. 3.5 +/- 1.1 per thousand, P men than in young men. Regardless of donor's age, nondisjunction is more prevalent than loss for both chromosome X and Y. The frequencies of observed simultaneous malsegregation were relatively higher than the expected, suggesting an association between malsegregation. These results indicated that in Chinese men, malsegregation of the sex chromosomes increases with age in an associated fashion, and nondisjunction accounts for the majority of spontaneous chromosome malsegregation.

  11. Caenorhabditis elegans cyclin B3 is required for multiple mitotic processes including alleviation of a spindle checkpoint-dependent block in anaphase chromosome segregation.

    Directory of Open Access Journals (Sweden)

    Gary M R Deyter

    2010-11-01

    Full Text Available The master regulators of the cell cycle are cyclin-dependent kinases (Cdks, which influence the function of a myriad of proteins via phosphorylation. Mitotic Cdk1 is activated by A-type, as well as B1- and B2-type, cyclins. However, the role of a third, conserved cyclin B family member, cyclin B3, is less well defined. Here, we show that Caenorhabditis elegans CYB-3 has essential and distinct functions from cyclin B1 and B2 in the early embryo. CYB-3 is required for the timely execution of a number of cell cycle events including completion of the MII meiotic division of the oocyte nucleus, pronuclear migration, centrosome maturation, mitotic chromosome condensation and congression, and, most strikingly, progression through the metaphase-to-anaphase transition. Our experiments reveal that the extended metaphase delay in CYB-3-depleted embryos is dependent on an intact spindle assembly checkpoint (SAC and results in salient defects in the architecture of holocentric metaphase chromosomes. Furthermore, genetically increasing or decreasing dynein activity results in the respective suppression or enhancement of CYB-3-dependent defects in cell cycle progression. Altogether, these data reveal that CYB-3 plays a unique, essential role in the cell cycle including promoting mitotic dynein functionality and alleviation of a SAC-dependent block in anaphase chromosome segregation.

  12. Mouse oocytes depend on BubR1 for proper chromosome segregation but not for prophase I arrest

    NARCIS (Netherlands)

    Touati, S.A.; Buffin, E.; Cladiere, D.; Hached, K.; Rachez, C.; Deursen, J.M.A. van; Wassmann, K.

    2015-01-01

    Mammalian female meiosis is error prone, with rates of meiotic chromosome missegregations strongly increasing towards the end of the reproductive lifespan. A strong reduction of BubR1 has been observed in oocytes of women approaching menopause and in ovaries of aged mice, which led to the hypothesis

  13. Mapping the Flavor Contributing Traits on "Fengwei Melon" (Cucumis melo L.) Chromosomes Using Parent Resequencing and Super Bulked-Segregant Analysis.

    Science.gov (United States)

    Zhang, Hong; Yi, Hongping; Wu, Mingzhu; Zhang, Yongbin; Zhang, Xuejin; Li, Meihua; Wang, Guangzhi

    2016-01-01

    We used a next-generation high-throughput sequencing platform to resequence the Xinguowei and Shouxing melon cultivars, the parents of Fengwei melon. We found 84% of the reads (under a coverage rate of "13×") placed on the reference genome DHL92. There were 2,550,000 single-nucleotide polymorphisms and 140,000 structural variations in the two genomes. We also identified 1,290 polymorphic genes between Xinguowei and Shouxing. We combined specific length amplified fragment sequencing (SLAF-seq) and bulked-segregant analysis (super-BSA) to analyze the two parents and the F2 extreme phenotypes. This combined method yielded 12,438,270 reads, 46,087 SLAF tags, and 4,480 polymorphic markers (average depth of 161.81×). There were six sweet trait-related regions containing 13 differential SLAF markers, and 23 sour trait-related regions containing 48 differential SLAF markers. We further fine-mapped the sweet trait to the genomic regions on chromosomes 6, 10, 11, and 12. Correspondingly, we mapped the sour trait-related genomic regions to chromosomes 2, 3, 4, 5, 9, and 12. Finally, we positioned nine of the 61 differential markers in the sweet and sour trait candidate regions on the parental genome. These markers corresponded to one sweet and eight sour trait-related genes. Our study provides a basis for marker-assisted breeding of desirable sweet and sour traits in Fengwei melons.

  14. Mapping the Flavor Contributing Traits on "Fengwei Melon" (Cucumis melo L. Chromosomes Using Parent Resequencing and Super Bulked-Segregant Analysis.

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    Full Text Available We used a next-generation high-throughput sequencing platform to resequence the Xinguowei and Shouxing melon cultivars, the parents of Fengwei melon. We found 84% of the reads (under a coverage rate of "13×" placed on the reference genome DHL92. There were 2,550,000 single-nucleotide polymorphisms and 140,000 structural variations in the two genomes. We also identified 1,290 polymorphic genes between Xinguowei and Shouxing. We combined specific length amplified fragment sequencing (SLAF-seq and bulked-segregant analysis (super-BSA to analyze the two parents and the F2 extreme phenotypes. This combined method yielded 12,438,270 reads, 46,087 SLAF tags, and 4,480 polymorphic markers (average depth of 161.81×. There were six sweet trait-related regions containing 13 differential SLAF markers, and 23 sour trait-related regions containing 48 differential SLAF markers. We further fine-mapped the sweet trait to the genomic regions on chromosomes 6, 10, 11, and 12. Correspondingly, we mapped the sour trait-related genomic regions to chromosomes 2, 3, 4, 5, 9, and 12. Finally, we positioned nine of the 61 differential markers in the sweet and sour trait candidate regions on the parental genome. These markers corresponded to one sweet and eight sour trait-related genes. Our study provides a basis for marker-assisted breeding of desirable sweet and sour traits in Fengwei melons.

  15. Accurate Chromosome Segregation at First Meiotic Division Requires AGO4, a Protein Involved in RNA-Dependent DNA Methylation in Arabidopsis thaliana.

    Science.gov (United States)

    Oliver, Cecilia; Santos, Juan Luis; Pradillo, Mónica

    2016-10-01

    The RNA-directed DNA methylation (RdDM) pathway is important for the transcriptional repression of transposable elements and for heterochromatin formation. Small RNAs are key players in this process by regulating both DNA and histone methylation. Taking into account that methylation underlies gene silencing and that there are genes with meiosis-specific expression profiles, we have wondered whether genes involved in RdDM could play a role during this specialized cell division. To address this issue, we have characterized meiosis progression in pollen mother cells from Arabidopsis thaliana mutant plants defective for several proteins related to RdDM. The most relevant results were obtained for ago4-1 In this mutant, meiocytes display a slight reduction in chiasma frequency, alterations in chromatin conformation around centromeric regions, lagging chromosomes at anaphase I, and defects in spindle organization. These abnormalities lead to the formation of polyads instead of tetrads at the end of meiosis, and might be responsible for the fertility defects observed in this mutant. Findings reported here highlight an involvement of AGO4 during meiosis by ensuring accurate chromosome segregation at anaphase I.

  16. The spatio-temporal dynamics of PKA activity profile during mitosis and its correlation to chromosome segregation.

    Science.gov (United States)

    Vandame, Pauline; Spriet, Corentin; Trinel, Dave; Gelaude, Armance; Caillau, Katia; Bompard, Coralie; Biondi, Emanuele; Bodart, Jean-François

    2014-01-01

    The cyclic adenosine monophosphate dependent kinase protein (PKA) controls a variety of cellular processes including cell cycle regulation. Here, we took advantages of genetically encoded FRET-based biosensors, using an AKAR-derived biosensor to characterize PKA activity during mitosis in living HeLa cells using a single-cell approach. We measured PKA activity changes during mitosis. HeLa cells exhibit a substantial increase during mitosis, which ends with telophase. An AKAREV T>A inactive form of the biosensor and H89 inhibitor were used to ascertain for the specificity of the PKA activity measured. On a spatial point of view, high levels of activity near to chromosomal plate during metaphase and anaphase were detected. By using the PKA inhibitor H89, we assessed the role of PKA in the maintenance of a proper division phenotype. While this treatment in our hands did not impaired cell cycle progression in a drastic manner, inhibition of PKA leads to a dramatic increase in chromososme misalignement on the spindle during metaphase that could result in aneuploidies. Our study emphasizes the insights that can be gained with genetically encoded FRET-based biosensors, which enable to overcome the shortcomings of classical methologies and unveil in vivo PKA spatiotemporal profiles in HeLa cells.

  17. Evolution and tinkering: what do a protein kinase, a transcriptional regulator and chromosome segregation/cell division proteins have in common?

    Science.gov (United States)

    Derouiche, Abderahmane; Shi, Lei; Kalantari, Aida; Mijakovic, Ivan

    2016-02-01

    In this study, we focus on functional interactions among multi-domain proteins which share a common evolutionary origin. The examples we develop are four Bacillus subtilis proteins, which all possess an ATP-binding Walker motif: the bacterial tyrosine kinase (BY-kinase) PtkA, the chromosome segregation protein Soj (ParA), the cell division protein MinD and a transcription regulator SalA. These proteins have arisen via duplication of the ancestral ATP-binding domain, which has undergone fusions with other functional domains in the process of divergent evolution. We point out that these four proteins, despite having very different physiological roles, engage in an unusually high number of binary functional interactions. Namely, MinD attracts Soj and PtkA to the cell pole, and in addition, activates the kinase function of PtkA. SalA also activates the kinase function of PtkA, and it gets phosphorylated by PtkA as well. The consequence of this phosphorylation is the activation of SalA as a transcriptional repressor. We hypothesize that these functional interactions remain preserved during divergent evolution and represent a constraint on the process of evolutionary "tinkering", brought about by fusions of different functional domains.

  18. Mutations reducing replication from R-loops suppress the defects of growth, chromosome segregation and DNA supercoiling in cells lacking topoisomerase I and RNase HI activity.

    Science.gov (United States)

    Usongo, Valentine; Martel, Makisha; Balleydier, Aurélien; Drolet, Marc

    2016-04-01

    R-loop formation occurs when the nascent RNA hybridizes with the template DNA strand behind the RNA polymerase. R-loops affect a wide range of cellular processes and their use as origins of replication was the first function attributed to them. In Escherichia coli, R-loop formation is promoted by the ATP-dependent negative supercoiling activity of gyrase (gyrA and gyrB) and is inhibited by topoisomerase (topo) I (topA) relaxing transcription-induced negative supercoiling. RNase HI (rnhA) degrades the RNA moiety of R-loops. The depletion of RNase HI activity in topA null mutants was previously shown to lead to extensive DNA relaxation, due to DNA gyrase inhibition, and to severe growth and chromosome segregation defects that were partially corrected by overproducing topo III (topB). Here, DNA gyrase assays in crude cell extracts showed that the ATP-dependent activity (supercoiling) of gyrase but not its ATP-independent activity (relaxation) was inhibited in topA null cells lacking RNase HI. To characterize the cellular event(s) triggered by the absence of RNase HI, we performed a genetic screen for suppressors of the growth defect of topA rnhA null cells. Suppressors affecting genes in replication (holC2::aph and dnaT18::aph) nucleotide metabolism (dcd49::aph), RNA degradation (rne59::aph) and fimbriae synthesis (fimD22::aph) were found to reduce replication from R-loops and to restore supercoiling, thus pointing to a correlation between R-loop-dependent replication in topA rnhA mutants and the inhibition of gyrase activity and growth. Interestingly, the position of fimD on the E. coli chromosome corresponds to the site of one of the five main putative origins of replication from R-loops in rnhA null cells recently identified by next-generation sequencing, thus suggesting that the fimD22::aph mutation inactivated one of these origins. Furthermore, we show that topo III overproduction is unable to complement the growth defect of topA rnhA null mutants at low

  19. Inactivation of Cdk1/Cyclin B in metaphase-arrested mouse FT210 cells induces exit from mitosis without chromosome segregation or cytokinesis and allows passage through another cell cycle.

    Science.gov (United States)

    Paulson, James R

    2007-04-01

    It is well known that inactivation of Cdk1/Cyclin B is required for cells to exit mitosis. The work reported here tests the hypothesis that Cdk1/Cyclin B inactivation is not only necessary but also sufficient to induce mitotic exit and reestablishment of the interphase state. This hypothesis predicts that inactivation of Cdk1 in metaphase-arrested cells will induce the M to G1-phase transition. It is shown that when mouse FT210 cells (in which Cdk1 is temperature-sensitive) are arrested in metaphase and then shifted to their non-permissive temperature, they rapidly exit mitosis as evidenced by reassembly of interphase nuclei, decondensation of chromosomes, and dephosphorylation of histones H1 and H3. The resulting interphase cells are functionally normal as judged by their ability to progress through another cell cycle. However, they have double the normal number of chromosomes because they previously bypassed anaphase, chromosome segregation, and cytokinesis. These results, taken together with other observations in the literature, strongly suggest that in mammalian cells, inactivation of Cdk1/cyclin B is the trigger for mitotic exit and reestablishment of the interphase state.

  20. Multicolor fluorescence in situ hybridization analysis of meiotic chromosome segregation in a 47,XYY male and a review of the literature.

    Science.gov (United States)

    Shi, Q; Martin, R H

    2000-07-03

    The frequencies of aneuploid and diploid sperm were determined in a 47,XYY male using multi-color fluorescence in situ hybridization (FISH) analysis, and compared with those from 10 control donors. A total of 30,078 sperm from the patient was scored, 15,044 by two-color FISH for chromosomes 13 and 21, and 15,034 by three-color FISH for the sex chromosomes using chromosome 1 as an internal autosomal control for diploidy and lack of hybridization. The frequencies of X-bearing (49.73%) and Y-bearing sperm (49.46%) in control males were not significantly different from the expected 50% (chi(2)-test for goodness of fit). The ratio of 24,X (50.60%) to 24, Y sperm (48.35%) in the patient, however, was significantly different from the controls (P = 0.0144, chi(2)-test for independence) and from the expected 1:1 ratio (P = 0.0055, chi(2)-test for goodness of fit). There was no significant increase in the frequency of diploid sperm when compared with the controls (chi(2)-test for independence). Significantly increased frequencies were found for 24,YY (0.07% vs. 0.02%, P = 0.0009) and 24,XY (0.44% vs. 0.29%, P = 0.0025), but not for 24,XX (0.05% vs. 0.05%, P > 0. 05), 24,+13 (0.07% vs. 0.07%, P > 0.05) or 24,+21 sperm (0.21% vs. 0. 18%, P > 0.05) in the 47,XYY male when compared with control donors (chi(2)-test for independence). Our results support the theory that loss of the extra Y chromosome occurs during spermatogenesis in most cells. In this XYY patient there was a significant increase in the frequency of sperm with sex chromosomal abnormalities but no suggestion of an inter-chromosomal effect on autosomes. All 3-color FISH studies in the literature demonstrate a significantly increased risk of gonosomal aneuploidy in XYY males, with the risk being on the order of 1%.

  1. A dynamic meiotic SUN belt includes the zygotene-stage telomere bouquet and is disrupted in chromosome segregation mutants of maize (Zea mays L..

    Directory of Open Access Journals (Sweden)

    Shaun Patrick Murphy

    2014-07-01

    Full Text Available The nuclear envelope (NE plays an essential role in meiotic telomere behavior and links the cytoplasm and nucleoplasm during homologous chromosome pairing and recombination in many eukaryotic species. Resident NE proteins including SUN (Sad-1/UNC-84 and KASH (Klarsicht/ANC-1/Syne-homology domain proteins are known to interact forming the Linker of Nucleoskeleton and Cytoskeleton (LINC complex that connects chromatin to the cytoskeleton. To investigate the possible cross-kingdom conservation of SUN protein functions in plant meiosis, we immunolocalized maize SUN2 using 3D microscopy of pollen mother cells from maize (Zea mays L., a large-genome plant model with a canonical NE zygotene-stage telomere bouquet. We detected SUN2 at the nuclear periphery and found that it exhibited a distinct belt-like structure that transitioned to a half-belt during the zygotene stage and back to a full belt during and beyond the pachytene stage. The zygotene-stage half-belt SUN structure was shown by 3D immuno-FISH to include the NE-associated telomere cluster that defines the bouquet stage and coincides with homologous chromosome synapsis. Microtubule and filamentous actin staining patterns did not show any obvious belt or a retracted-like structure other than a general enrichment of tubulin staining distributed widely around the nucleus and throughout the cytoplasm. Genetic disruption of the meiotic SUN belt staining patterns with three different meiosis-specific mutants, desynaptic (dy1, asynaptic1 (as1, and divergent spindle1 (dv1 provides additional evidence for the role of the nuclear envelope in meiotic chromosome behavior. Taking into account all of the observations from this study, we propose that the maize SUN belt is directly or indirectly involved in meiotic telomere dynamics, chromosome synapsis, and possibly integration of signals and forces across the meiotic prophase nuclear envelope.

  2. From equator to pole: splitting chromosomes in mitosis and meiosis.

    Science.gov (United States)

    Duro, Eris; Marston, Adèle L

    2015-01-15

    During eukaryotic cell division, chromosomes must be precisely partitioned to daughter cells. This relies on a mechanism to move chromosomes in defined directions within the parental cell. While sister chromatids are segregated from one another in mitosis and meiosis II, specific adaptations enable the segregation of homologous chromosomes during meiosis I to reduce ploidy for gamete production. Many of the factors that drive these directed chromosome movements are known, and their molecular mechanism has started to be uncovered. Here we review the mechanisms of eukaryotic chromosome segregation, with a particular emphasis on the modifications that ensure the segregation of homologous chromosomes during meiosis I.

  3. Segregation of Polymers in Confined Spaces

    CERN Document Server

    Liu, Ya

    2009-01-01

    We investigate the motion of two overlapping polymers with self-avoidance confined in a narrow 2d box. A statistical model is constructed using blob free-energy arguments. We find spontaneous segregation under the condition: $L > R_{//}$, and mixing under $L < R_{//}$, where L is the length of the box, and $R_{//}$ the polymer extension in an infinite slit. Segregation time scales are determined by solving a mean first-passage time problem, and by performing Monte Carlo simulations. Predictions of the two methods show good agreement. Our results may elucidate a driving force for chromosomes segregation in bacteria.

  4. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

    OpenAIRE

    Maia André F; Vader Gerben; Lens Susanne MA

    2008-01-01

    Abstract During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension). In ...

  5. Meiosis I: When Chromosomes Undergo Extreme Makeover

    OpenAIRE

    Miller, Matthew P; Amon, Angelika; Ünal, Elçin

    2013-01-01

    The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserves the chromosome complement of the progenitor cell. In co...

  6. Chromosome segregation: Samurai separation of Siamese sisters.

    Science.gov (United States)

    Glotzer, M

    1999-07-15

    How do cells ensure that sister chromatids are precisely partitioned in mitosis? New studies on budding yeast have revealed that sister chromatid separation at anaphase requires endoproteolytic cleavage of a protein that maintains the association between sister chromatids.

  7. Bacillus subtilis chromosome organization oscillates between two distinct patterns

    OpenAIRE

    Wang, Xindan; Montero Llopis, Paula; Rudner, David Z.

    2014-01-01

    In bacteria, faithful and efficient DNA segregation is intimately linked to the spatial organization of the chromosome. Two distinct organization patterns have been described for bacterial chromosomes (ori-ter and left-ori-right) that appear to arise from distinct segregation mechanisms. Here, we show that the Bacillus subtilis chromosome oscillates between them during a replication–segregation cycle. Our data further suggest that the highly conserved condensin complex and the parABS partitio...

  8. Chromosome choreography: the meiotic ballet.

    Science.gov (United States)

    Page, Scott L; Hawley, R Scott

    2003-08-08

    The separation of homologous chromosomes during meiosis in eukaryotes is the physical basis of Mendelian inheritance. The core of the meiotic process is a specialized nuclear division (meiosis I) in which homologs pair with each other, recombine, and then segregate from each other. The processes of chromosome alignment and pairing allow for homolog recognition. Reciprocal meiotic recombination ensures meiotic chromosome segregation by converting sister chromatid cohesion into mechanisms that hold homologous chromosomes together. Finally, the ability of sister kinetochores to orient to a single pole at metaphase I allows the separation of homologs to two different daughter cells. Failures to properly accomplish this elegant chromosome dance result in aneuploidy, a major cause of miscarriage and birth defects in human beings.

  9. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation▿ †

    OpenAIRE

    Shebelut, Conrad W.; Jensen, Rasmus B.; Gitai, Zemer

    2008-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated.

  10. Heteromorphic sex chromosomes: navigating meiosis without a homologous partner.

    Science.gov (United States)

    Checchi, Paula M; Engebrecht, Joanne

    2011-09-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have been modified in many different ways to ensure segregation of heteromorphic sex chromosomes at the first meiotic division. Additionally, an almost universal feature of heteromorphic sex chromosomes during meiosis is transcriptional silencing, or meiotic sex chromosome inactivation, an essential process proposed to prevent expression of genes deleterious to meiosis in the heterogametic sex as well as to shield unpaired sex chromosomes from recognition by meiotic checkpoints. Comparative analyses of the meiotic behavior of sex chromosomes in nematodes, mammals, and birds reveal important conserved features as well as provide insight into sex chromosome evolution.

  11. Dicentric chromosomes: unique models to study centromere function and inactivation

    OpenAIRE

    Kaitlin M Stimpson; Matheny, Justyne E.; Sullivan, Beth A.

    2012-01-01

    Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell divisi...

  12. Chromosome condensation: weaving an untangled web.

    Science.gov (United States)

    Thadani, Rahul; Uhlmann, Frank

    2015-08-03

    The compaction of diffuse interphase chromatin into stable mitotic chromosomes enables the segregation of replicated DNA to daughter cells. Two new studies characterise, both in vivo and in vitro, the essential contribution of the vertebrate condensin complex to chromosome organisation.

  13. Building bridges within the bacterial chromosome.

    Science.gov (United States)

    Song, Dan; Loparo, Joseph J

    2015-03-01

    All organisms must dramatically compact their genomes to accommodate DNA within the cell. Bacteria use a set of DNA-binding proteins with low sequence specificity called nucleoid-associated proteins (NAPs) to assist in chromosome condensation and organization. By bending or bridging DNA, NAPs also facilitate chromosome segregation and regulate gene expression. Over the past decade, emerging single-molecule and chromosome conformation capture techniques have investigated the molecular mechanisms by which NAPs remodel and organize the bacterial chromosome. In this review we describe how such approaches reveal the biochemical mechanisms of three NAPs that are believed to facilitate DNA bridging: histone-like nucleoid structuring protein (H-NS), ParB, and structural maintenance of chromosomes (SMC). These three proteins form qualitatively different DNA bridges, leading to varied effects on transcription and chromosome segregation.

  14. Condensin-Based Chromosome Organization from Bacteria to Vertebrates.

    Science.gov (United States)

    Hirano, Tatsuya

    2016-02-25

    Condensins are large protein complexes that play a central role in chromosome organization and segregation in the three domains of life. They display highly characteristic, rod-shaped structures with SMC (structural maintenance of chromosomes) ATPases as their core subunits and organize large-scale chromosome structure through active mechanisms. Most eukaryotic species have two distinct condensin complexes whose balanced usage is adapted flexibly to different organisms and cell types. Studies of bacterial condensins provide deep insights into the fundamental mechanisms of chromosome segregation. This Review surveys both conserved features and rich variations of condensin-based chromosome organization and discusses their evolutionary implications.

  15. Spatial organization and segregation of two self-avoiding polymers in a closed cylindrical pore

    Science.gov (United States)

    Jung, Youngkyun; Ha, Bae-Yeun

    2010-03-01

    We present some results on the spatial organization and segregation of two self-avoiding polymers trapped inside a closed cylindrical pore, obtained using molecular dynamics simulations. Closed cylindrical confinement is shown to play a unique role in influencing chain miscibility and segregation dynamics. Our diagram for chain miscibility shows that under strong confinement chains segregate better, if they are shorter and the con?ning space is more asymmetric; when applied to bacterial chromosomes, it implies that chromosome miscibility depends on how they are structured inside the cell. Finally, longitudinal con?nement is also shown to have nontrivial effects on segregation dynamics; it can signi?cantly slow down segregation despite a shorter distance for each chain to travel to partially segregate.

  16. GSK-3 inhibitors induce chromosome instability

    Directory of Open Access Journals (Sweden)

    Staples Oliver D

    2007-08-01

    Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.

  17. Commentary: Genger Segregation in Childhood.

    Science.gov (United States)

    Maccoby, Eleanor E.

    1994-01-01

    Provides an overview of the preceding articles in this journal issue. Considers the timing of gender segregation, compatibility between play styles and gender segregation, possible physiological processes underlying gender segregation in play, children's cognitive knowledge about gender, and the consequences of gender segregation. (BAC)

  18. Sex chromosome rearrangements in Polyphaga beetles.

    Science.gov (United States)

    Dutrillaux, A M; Dutrillaux, B

    2009-01-01

    The presence of a parachute sex chromosome bivalent (Xyp) at metaphase I of male meiosis is a well-known characteristic of Coleoptera, present in almost all families of this order and assumed to represent their ancestral sex chromosome formula. Sex chromosomes appear to be manifold more frequently involved in inter-chromosomal rearrangements than the average of the nine autosomal pairs usually forming their karyotype. This leads to various formulae such as neo-sex, multiple sex and perhaps unique sex chromosomes. These rearrangements alter the intimate association between sex chromosomes and nucleolar proteins, which are usual components of the Xyp. Different situations, selected in a series of 125 mitotic and meiotic cytogenetic studies of Polyphaga beetle species, are reported and discussed, with the aim to improve our knowledge on the mechanisms of sex chromosome rearrangements, the relationships with nucleoli and the consequences on dosage compensation and chromosome segregation.

  19. Understanding Segregation Processes

    Science.gov (United States)

    Bruch, Elizabeth

    There is growing consensus that living in neighborhoods of concentrated poverty increases the likelihood of social problems such as teenage parenthood, drug and alcohol use, crime victimization, and chronic unemployment. Neighborhood inequality is also implicated in studies of enduring race/ethnic health disparities, and there are recent moves to broaden the definition of health care policy to policies targeting social inequality (Mechanic 2007). Residential segregation affects health outcomes in several different ways. First, income, education, and occupation are all strongly related to health (Adler and Newman 2002). Segregation is a key mechanism through which socioeconomic inequality is perpetuated and reinforced, as it hinders the upward mobility of disadvantaged groups by limiting their educational and employment opportunities. Second, segregation increases minority exposure to unhealthy neighborhood environments. Residential segregation creates areas with concentrated poverty and unemployment, both of which are key factors that predict violence and create racial differences in homicide (Samson and Wilson 1995). Neighborhood characteristics, such as exposure to environmental hazards, fear of violence, and access to grocery stores, affect health risks and health behaviors (Cheadle et al. 1991). Tobacco and alcohol industries also advertise their products disproportionately in poor, minority areas (Moore, Williams, and Qualls 1996). Finally, residential segregation leads to inequalitie in health care resources, which contributes to disparities in quality of treatment (Smedley, Stith, and Nelson 2002).

  20. Measuring Inequality and Segregation

    CERN Document Server

    Roberto, Elizabeth

    2015-01-01

    In this paper, I introduce the Divergence Index, a conceptually intuitive and methodologically rigorous measure of inequality and segregation. The index measures the difference between a distribution of interest and another empirical, theoretical, or normative distribution. The Divergence Index provides flexibility in specifying a theoretically meaningful basis for evaluating inequality. It evaluates how surprising an empirical distribution is given a theoretical distribution that represents equality. I demonstrate the unique features of the new measure, as well as deriving its mathematical equivalence with Theil's Inequality Index and the Information Theory Index. I compare the dynamics of the measures using simulated data, and an empirical analysis of racial residential segregation in the Detroit, MI, metro area. The Information Theory Index has become the gold standard for decomposition analyses of segregation. I show that although the Information Theory Index can be decomposed for subareas, it is misleadi...

  1. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  2. Heteromorphic Sex Chromosomes: Navigating Meiosis without a Homologous Partner

    OpenAIRE

    Checchi, Paula M.; Engebrecht, JoAnne

    2011-01-01

    Accurate chromosome segregation during meiosis relies on homology between the maternal and paternal chromosomes. Yet by definition, sex chromosomes of the heterogametic sex lack a homologous partner. Recent studies in a number of systems have shed light on the unique meiotic behavior of heteromorphic sex chromosomes, and highlight both the commonalities and differences in divergent species. During meiotic prophase, the homology-dependent processes of pairing, synapsis, and recombination have ...

  3. Plasmid segregation mechanisms

    DEFF Research Database (Denmark)

    Ebersbach, Gitte; Gerdes, Kenn; Charbon, Gitte Ebersbach

    2005-01-01

    Bacterial plasmids encode partitioning (par) loci that ensure ordered plasmid segregation prior to cell division. par loci come in two types: those that encode actin-like ATPases and those that encode deviant Walker-type ATPases. ParM, the actin-like ATPase of plasmid R1, forms dynamic filaments ...

  4. Bacterial scaffold directs pole-specific centromere segregation.

    Science.gov (United States)

    Ptacin, Jerod L; Gahlmann, Andreas; Bowman, Grant R; Perez, Adam M; von Diezmann, Alexander R S; Eckart, Michael R; Moerner, W E; Shapiro, Lucy

    2014-05-13

    Bacteria use partitioning systems based on the ParA ATPase to actively mobilize and spatially organize molecular cargoes throughout the cytoplasm. The bacterium Caulobacter crescentus uses a ParA-based partitioning system to segregate newly replicated chromosomal centromeres to opposite cell poles. Here we demonstrate that the Caulobacter PopZ scaffold creates an organizing center at the cell pole that actively regulates polar centromere transport by the ParA partition system. As segregation proceeds, the ParB-bound centromere complex is moved by progressively disassembling ParA from a nucleoid-bound structure. Using superresolution microscopy, we show that released ParA is recruited directly to binding sites within a 3D ultrastructure composed of PopZ at the cell pole, whereas the ParB-centromere complex remains at the periphery of the PopZ structure. PopZ recruitment of ParA stimulates ParA to assemble on the nucleoid near the PopZ-proximal cell pole. We identify mutations in PopZ that allow scaffold assembly but specifically abrogate interactions with ParA and demonstrate that PopZ/ParA interactions are required for proper chromosome segregation in vivo. We propose that during segregation PopZ sequesters free ParA and induces target-proximal regeneration of ParA DNA binding activity to enforce processive and pole-directed centromere segregation, preventing segregation reversals. PopZ therefore functions as a polar hub complex at the cell pole to directly regulate the directionality and destination of transfer of the mitotic segregation machine.

  5. Meiosis I: when chromosomes undergo extreme makeover.

    Science.gov (United States)

    Miller, Matthew P; Amon, Angelika; Ünal, Elçin

    2013-12-01

    The ultimate success of cell division relies on the accurate partitioning of the genetic material. Errors in this process occur in nearly all tumors and are the leading cause of miscarriages and congenital birth defects in humans. Two cell divisions, mitosis and meiosis, use common as well as unique mechanisms to ensure faithful chromosome segregation. In mitosis, alternating rounds of DNA replication and chromosome segregation preserve the chromosome complement of the progenitor cell. In contrast, during meiosis two consecutive rounds of nuclear division, meiosis I and meiosis II, follow a single round of DNA replication to reduce the chromosome complement by half. Meiosis likely evolved through changes to the mitotic cell division program. This review will focus on the recent findings describing the modifications that transform mitosis into meiosis.

  6. Estimating tempo and mode of Y chromosome turnover: explaining Y chromosome loss with the fragile Y hypothesis.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2014-06-01

    Chromosomal sex determination is phylogenetically widespread, having arisen independently in many lineages. Decades of theoretical work provide predictions about sex chromosome differentiation that are well supported by observations in both XY and ZW systems. However, the phylogenetic scope of previous work gives us a limited understanding of the pace of sex chromosome gain and loss and why Y or W chromosomes are more often lost in some lineages than others, creating XO or ZO systems. To gain phylogenetic breadth we therefore assembled a database of 4724 beetle species' karyotypes and found substantial variation in sex chromosome systems. We used the data to estimate rates of Y chromosome gain and loss across a phylogeny of 1126 taxa estimated from seven genes. Contrary to our initial expectations, we find that highly degenerated Y chromosomes of many members of the suborder Polyphaga are rarely lost, and that cases of Y chromosome loss are strongly associated with chiasmatic segregation during male meiosis. We propose the "fragile Y" hypothesis, that recurrent selection to reduce recombination between the X and Y chromosome leads to the evolution of a small pseudoautosomal region (PAR), which, in taxa that require XY chiasmata for proper segregation during meiosis, increases the probability of aneuploid gamete production, with Y chromosome loss. This hypothesis predicts that taxa that evolve achiasmatic segregation during male meiosis will rarely lose the Y chromosome. We discuss data from mammals, which are consistent with our prediction.

  7. Sexual maldevelopment and sex reversal, chromosomal causes.

    Science.gov (United States)

    Magenis, R Ellen

    2006-01-01

    The SRY gene on the Y chromosome is the testis determining factor (TDF). It is therefore the initial male determining factor. However, phenotypic sex determination includes a cascade of genes located on autosomes as well as sex chromosomes. Aberrations of these genes may cause sexual maldevelopment or sex reversal. Abnormalities may include single gene mutations and gene loss or gain-changes may involve only sex organs or may be part of syndromes. These changes may also arise as chromosome abnormalities involving contiguous genes. Eight cases with chromosomal abnormalities involving different causative mechanisms are described herein. The most common cause is nondisjunction, including loss or gain of sex chromosomes. Less common causes are mispairing and crossing over in meiosis, chromosome breaks with repair, nonhomologous pairing due to low copy repeats and crossing over, and translocation (familial or de novo) with segregation. Cases include: [see: text].

  8. Patterns of Residential Segregation.

    Directory of Open Access Journals (Sweden)

    Rémi Louf

    Full Text Available The spatial distribution of income shapes the structure and organisation of cities and its understanding has broad societal implications. Despite an abundant literature, many issues remain unclear. In particular, all definitions of segregation are implicitely tied to a single indicator, usually rely on an ambiguous definition of income classes, without any consensus on how to define neighbourhoods and to deal with the polycentric organization of large cities. In this paper, we address all these questions within a unique conceptual framework. We avoid the challenge of providing a direct definition of segregation and instead start from a definition of what segregation is not. This naturally leads to the measure of representation that is able to identify locations where categories are over- or underrepresented. From there, we provide a new measure of exposure that discriminates between situations where categories co-locate or repel one another. We then use this feature to provide an unambiguous, parameter-free method to find meaningful breaks in the income distribution, thus defining classes. Applied to the 2014 American Community Survey, we find 3 emerging classes-low, middle and higher income-out of the original 16 income categories. The higher-income households are proportionally more present in larger cities, while lower-income households are not, invalidating the idea of an increased social polarisation. Finally, using the density-and not the distance to a center which is meaningless in polycentric cities-we find that the richer class is overrepresented in high density zones, especially for larger cities. This suggests that density is a relevant factor for understanding the income structure of cities and might explain some of the differences observed between US and European cities.

  9. Modulating crossover positioning by introducing large structural changes in chromosomes

    NARCIS (Netherlands)

    Ederveen, A.; Lai, Y.; Van Driel, M.A.; Gerats, T.; Peters, J.L.

    2015-01-01

    Background Crossing over assures the correct segregation of the homologous chromosomes to both poles of the dividing meiocyte. This exchange of DNA creates new allelic combinations thus increasing the genetic variation present in offspring. Crossovers are not uniformly distributed along chromosomes;

  10. Homolog pairing and segregation in Drosophila meiosis.

    Science.gov (United States)

    McKee, B D

    2009-01-01

    Pairing of homologous chromosomes is fundamental to their reliable segregation during meiosis I and thus underlies sexual reproduction. In most eukaryotes homolog pairing is confined to prophase of meiosis I and is accompanied by frequent exchanges, known as crossovers, between homologous chromatids. Crossovers give rise to chiasmata, stable interhomolog connectors that are required for bipolar orientation (orientation to opposite poles) of homologs during meiosis I. Drosophila is unique among model eukaryotes in exhibiting regular homolog pairing in mitotic as well as meiotic cells. I review the results of recent molecular studies of pairing in both mitosis and meiosis in Drosophila. These studies show that homolog pairing is continuous between pre-meiotic mitosis and meiosis but that pairing frequencies and patterns are altered during the mitotic-meiotic transition. They also show that, with the exception of X-Y pairing in male meiosis, which is mediated specifically by the 240-bp rDNA spacer repeats, chromosome pairing is not restricted to specific sites in either mitosis or meiosis. Instead, virtually all chromosome regions, both heterochromatic and euchromatic, exhibit autonomous pairing capacity. Mutations that reduce the frequencies of both mitotic and meiotic pairing have been recently described, but no mutations that abolish pairing completely have been discovered, and the genetic control of pairing in Drosophila remains to be elucidated.

  11. Sister chromatid segregation in meiosis II: deprotection through phosphorylation.

    Science.gov (United States)

    Wassmann, Katja

    2013-05-01

    Meiotic divisions (meiosis I and II) are specialized cell divisions to generate haploid gametes. The first meiotic division with the separation of chromosomes is named reductional division. The second division, which takes place immediately after meiosis I without intervening S-phase, is equational, with the separation of sister chromatids, similar to mitosis. This meiotic segregation pattern requires the two-step removal of the cohesin complex holding sister chromatids together: cohesin is removed from chromosome arms that have been subjected to homologous recombination in meiosis I and from the centromere region in meiosis II. Cohesin in the centromere region is protected from removal in meiosis I, but this protection has to be removed--deprotected--for sister chromatid segregation in meiosis II. Whereas the mechanisms of cohesin protection are quite well understood, the mechanisms of deprotection have been largely unknown until recently. In this review I summarize our current knowledge on cohesin deprotection.

  12. Towards understanding the molecular basis of bacterial DNA segregation

    DEFF Research Database (Denmark)

    Leonard, Thomas A.; Møller-Jensen, Jakob; Löwe, Jan

    2005-01-01

    Bacteria ensure the fidelity of genetic inheritance by the coordinated control of chromosome segregation and cell division. Here, we review the molecules and mechanisms that govern the correct subcellular positioning and rapid separation of newly replicated chromosomes and plasmids towards the cell...... poles and, significantly, the emergence of mitotic-like machineries capable of segregating plasmid DNA. We further describe surprising similarities between proteins involved in DNA partitioning (ParA/ParB) and control of cell division (MinD/MinE), suggesting a mechanism for intracellular positioning...... common to the two processes. Finally, we discuss the role that the bacterial cytoskeleton plays in DNA partitioning and the missing link between prokaryotes and eukaryotes that is bacterial mechano-chemical motor proteins. Udgivelsesdato: Mar 29...

  13. Plasmid and chromosome partitioning: surprises from phylogeny

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Bugge Jensen, Rasmus

    2000-01-01

    Plasmids encode partitioning genes (par) that are required for faithful plasmid segregation at cell division. Initially, par loci were identified on plasmids, but more recently they were also found on bacterial chromosomes. We present here a phylogenetic analysis of par loci from plasmids and chr...

  14. Proteomic analysis of human metaphase chromosomes reveals Topoisomerase II alpha as an Aurora B substrate

    DEFF Research Database (Denmark)

    Morrison, Ciaran; Henzing, Alexander J; Jensen, Ole Nørregaard;

    2002-01-01

    The essential Aurora B kinase is a chromosomal passenger protein that is required for mitotic chromosome alignment and segregation. Aurora B function is dependent on the chromosome passenger, INCENP. INCENP, in turn, requires sister chromatid cohesion for its appropriate behaviour. Relatively few...

  15. Analysis of the terminus region of the Caulobacter crescentus chromosome and identification of the dif site

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    The terminus region of the Caulobacter crescentus chromosome and the dif chromosome dimer resolution site were characterized. The Caulobacter genome contains skewed sequences that abruptly switch strands at dif and may have roles in chromosome maintenance and segregation. Absence of dif or the Xer...

  16. Modeling Chromosomes

    Science.gov (United States)

    Robertson, Carol

    2016-01-01

    Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…

  17. Patterns of residential segregation

    CERN Document Server

    Louf, Rémi

    2015-01-01

    The spatial distribution of income shapes the structure and organisation of cities and its understanding has broad societal implications. Despite an abundant literature, many issues remain however unclear: there is no clear definition of what segregation is, no unambiguous definition of income classes, no clear way to identify neighborhoods, and no method to deal with the polycentric organization of large cities. In this paper, we address all these questions within a unique theoretical framework. We assume that households belonging to the same class tend to live close to each other, and households from different classes tend to avoid one another. Applied to the US 2000 Census Income data, 3 distinct classes emerge from the clustering of the original 16 income classes. Using these unambiguously defined classes, we cluster together contiguous similar areas and find that the number of clusters for each category scales with the city population, an effect that is more pronounced for rich households. Finally, using...

  18. Shaping Segregation: Convexity vs. concavity

    NARCIS (Netherlands)

    Gonzalez, S.; Windows-Yule, C.R.; Luding, S.; Parker, D.J.; Thornton, A.R.

    2014-01-01

    Controlling segregation is both a practical and a theoretical challenge. In this Letter we demonstrate a manner in which rotation-induced segregation may be controlled by altering the geometry of the rotating containers in which granular systems are housed. Using a novel drum design comprising conca

  19. Shaping mitotic chromosomes: From classical concepts to molecular mechanisms.

    Science.gov (United States)

    Kschonsak, Marc; Haering, Christian H

    2015-07-01

    How eukaryotic genomes are packaged into compact cylindrical chromosomes in preparation for cell divisions has remained one of the major unsolved questions of cell biology. Novel approaches to study the topology of DNA helices inside the nuclei of intact cells, paired with computational modeling and precise biomechanical measurements of isolated chromosomes, have advanced our understanding of mitotic chromosome architecture. In this Review Essay, we discuss - in light of these recent insights - the role of chromatin architecture and the functions and possible mechanisms of SMC protein complexes and other molecular machines in the formation of mitotic chromosomes. Based on the information available, we propose a stepwise model of mitotic chromosome condensation that envisions the sequential generation of intra-chromosomal linkages by condensin complexes in the context of cohesin-mediated inter-chromosomal linkages, assisted by topoisomerase II. The described scenario results in rod-shaped metaphase chromosomes ready for their segregation to the cell poles.

  20. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Directory of Open Access Journals (Sweden)

    Judit Pampalona

    Full Text Available Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  1. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Science.gov (United States)

    Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

    2016-01-01

    Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  2. Release of chromosomes from the nuclear envelope: a universal mechanism for eukaryotic mitosis?

    Science.gov (United States)

    Kanoh, Junko

    2013-01-01

    Multiple domains of chromosomes are associated with the nuclear envelope (NE) in interphase. The association between chromosomes and the NE is involved in a variety of chromosomal reactions, such as gene expression and DNA repair. However, efficient chromosome movements are required for the fidelity of chromosome segregation in mitosis. Most higher eukaryotes perform open mitosis, in which the NE is broken down, enabling chromosomes to be released from the NE as well as spindle microtubules to access to kinetochores. By contrast, lower eukaryotes, such as Schizosaccharomyces pombe, perform closed mitosis, during which NE breakdown does not occur. In S. pombe, telomeres are tethered to the NE in interphase. Phosphorylation of the telomere-binding protein Rap1 at M phase promotes transient dissociation of telomeres from the NE, facilitating the faithful chromosome segregation. These findings imply a common mechanism for genome stability via the dissociation of chromosomes from the NE in eukaryotic mitosis.

  3. The tricky path to recombining X and Y chromosomes in meiosis.

    Science.gov (United States)

    Kauppi, Liisa; Jasin, Maria; Keeney, Scott

    2012-09-01

    Sex chromosomes are the Achilles' heel of male meiosis in mammals. Mis-segregation of the X and Y chromosomes leads to sex chromosome aneuploidies, with clinical outcomes such as infertility and Klinefelter syndrome. Successful meiotic divisions require that all chromosomes find their homologous partner and achieve recombination and pairing. Sex chromosomes in males of many species have only a small region of homology (the pseudoautosomal region, PAR) that enables pairing. Until recently, little was known about the dynamics of recombination and pairing within mammalian X and Y PARs. Here, we review our recent findings on PAR behavior in mouse meiosis. We uncovered unexpected differences between autosomal chromosomes and the X-Y chromosome pair, namely that PAR recombination and pairing occurs later, and is under different genetic control. These findings imply that spermatocytes have evolved distinct strategies that ensure successful X-Y recombination and chromosome segregation.

  4. Can topology reshape segregation patterns?

    CERN Document Server

    Gandica, Yerali; Carletti, Timoteo

    2015-01-01

    We consider a metapopulation version of the Schelling model of segregation over several complex networks and lattice. We show that the segregation process is topology independent and hence it is intrinsic to the individual tolerance. The role of the topology is to fix the places where the segregation patterns emerge. In addition we address the question of the time evolution of the segregation clusters, resulting from different dynamical regimes of a coarsening process, as a function of the tolerance parameter. We show that the underlying topology may alter the early stage of the coarsening process, once large values of the tolerance are used, while for lower ones a different mechanism is at work and it results to be topology independent.

  5. Mitotic chromosome compaction via active loop extrusion

    Science.gov (United States)

    Goloborodko, Anton; Imakaev, Maxim; Marko, John; Mirny, Leonid; MIT-Northwestern Team

    During cell division, two copies of each chromosome are segregated from each other and compacted more than hundred-fold into the canonical X-shaped structures. According to earlier microscopic observations and the recent Hi-C study, chromosomes are compacted into arrays of consecutive loops of ~100 kilobases. Mechanisms that lead to formation of such loop arrays are largely unknown. Here we propose that, during cell division, chromosomes can be compacted by enzymes that extrude loops on chromatin fibers. First, we use computer simulations and analytical modeling to show that a system of loop-extruding enzymes on a chromatin fiber self-organizes into an array of consecutive dynamic loops. Second, we model the process of loop extrusion in 3D and show that, coupled with the topo II strand-passing activity, it leads to robust compaction and segregation of sister chromatids. This mechanism of chromosomal condensation and segregation does not require additional proteins or specific DNA markup and is robust against variations in the number and properties of such loop extruding enzymes. Work at NU was supported by the NSF through Grants DMR-1206868 and MCB-1022117, and by the NIH through Grants GM105847 and CA193419. Work at MIT was supported by the NIH through Grants GM114190 R01HG003143.

  6. Functions of spindle check-point and its relationship to chromosome instability

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    It is generally believed that the equal distribution of genetic materials to two daughter cells during mitosis is the key to cell health and development. During the dynamic process, spindle checkpoint plays a very important role in chromosome movements and final sister chromatid separation. The equal and precise segregation of chromosomes contributes to the genomic stability while aberrant separations result in chromosome instability that causes pathogenesis of certain diseases such as Down's syndrome and cancers. Kinetochore and its regulatory proteins consist of the spindle checkpoint and determine the spatial and temporal orders of chromosome segregation.

  7. Chromosome assortment in Saccharum.

    Science.gov (United States)

    Al-Janabi, S M; Honeycutt, R J; Sobral, B W

    1994-12-01

    Recent work has revealed random chromosome pairing and assortment in Saccharum spontaneum L., the most widely distributed, and morphologically and cytologically variable of the species of Saccharum. This conclusion was based on the analysis of a segregating population from across between S. spontaneum 'SES 208' and a spontaneously-doubled haploid of itself, derived from anther culture. To determine whether polysomic inheritance is common in Saccharum and whether it is observed in a typical biparental cross, we studied chromosome pairing and assortment in 44 progeny of a cross between euploid, meiotically regular, 2n=80 forms of Saccharum officinarum 'LA Purple' and Saccharum robustum ' Mol 5829'. Papuan 2n=80 forms of S. robustum have been suggested as the immediate progenitor species for cultivated sugarcane (S. officinarum). A total of 738 loci in LA Purple and 720 loci in Mol 5829 were amplified and typed in the progeny by arbitrarily primed PCR using 45 primers. Fifty and 33 single-dose polymorphisms were identified in the S. officinarum and S. robustum genomes, respectively (χ 2 at 98%). Linkage analysis of single-dose polymorphisms in both genomes revealed linkages in repulsion and coupling phases. In the S. officinarum genome, a map hypothesis gave 7 linkage groups with 17 linked and 33 unlinked markers. Four of 13 pairwise linkages were in repulsion phase and 9 were in coupling phase. In the S. robustum genome, a map hypothesis gave 5 linkage groups, defined by 12 markers, with 21 markers unlinked, and 2 of 9 pairwise linkages were in repulsion phase. Therefore, complete polysomic inheritance was not observed in either species, suggesting that chromosomal behavior is different from that observed by linkage analysis of over 500 markers in the S. spontaneum map. Implications of this finding for evolution and breeding are discussed.

  8. Chromosome number reports in Astragalus sect. Onobrychoidei (Fabaceae from Iran

    Directory of Open Access Journals (Sweden)

    Massoud Ranjbar

    2015-01-01

    Full Text Available In this study, original mitotic chromosome counts have been presented for 10 populations belonging to 6 species of Astragalus sect. Onobrychoidei: A. aduncus, A. arguricus, A. cancellatus, A. lilacinus and A. vegetus. All taxa were diploid and possessed 2n = 2x = 16 chromosome number, consistent with the proposed base number of x = 8. In addition, meiotic studies revealed chromosome number of 2n = 2x = 16 for A. aduncus21 and A. brevidens and also 2n = 4x = 32 for A. vegetus99. Although this taxon displayed regular bivalent pairing and chromosome segregation at meiosis, some abnormalities were observed.

  9. Synthetic chromosomes.

    Science.gov (United States)

    Schindler, Daniel; Waldminghaus, Torsten

    2015-11-01

    What a living organism looks like and how it works and what are its components-all this is encoded on DNA, the genetic blueprint. Consequently, the way to change an organism is to change its genetic information. Since the first pieces of recombinant DNA have been used to transform cells in the 1970s, this approach has been enormously extended. Bigger and bigger parts of the genetic information have been exchanged or added over the years. Now we are at a point where the construction of entire chromosomes becomes a reachable goal and first examples appear. This development leads to fundamental new questions, for example, about what is possible and desirable to build or what construction rules one needs to follow when building synthetic chromosomes. Here we review the recent progress in the field, discuss current challenges and speculate on the appearance of future synthetic chromosomes.

  10. A physical approach to segregation and folding of the Caulobacter crescentus genome

    NARCIS (Netherlands)

    Dame, R.T.; Tark-Dame, M.; Schiessel, H

    2011-01-01

    Bacterial genomes are functionally organized. This organization is dynamic and globally changing throughout the cell cycle. Upon initiation of replication of the chromosome, the two origins segregate and move towards their new location taking along the newly replicated genome. Caulobacter crescentus

  11. Segregation distortion in chicken and the evolutionary consequences of female meiotic drive in birds

    DEFF Research Database (Denmark)

    Axelsson, Erik Gunnar; Albrechtsen, Anders; Van, A. P.

    2010-01-01

    As all four meiotic products give rise to sperm in males, female meiosis result in a single egg in most eukaryotes. Any genetic element with the potential to influence chromosome segregation, so that it is preferentially included in the egg, should therefore gain a transmission advantage; a process...

  12. Heats of Segregation and Segregation Profiles of BCC Metals

    Science.gov (United States)

    Good, Brian S.; Bozzolo, Guillermo

    2002-01-01

    The composition of metal alloy surfaces is often different from that of the bulk. Some alloys exhibit surface segregation, where one or more species reside preferentially at or near the surface. A detailed understanding of this behavior is necessary to correctly model such phenomena as adhesion or catalysis. Several phenomenological approaches to the problem have been put forward, falling into two broad categories: Thermodynamic approaches, where the equilibrium distribution of chemical species is computed. Atomistic approaches, where the tendency of a species to segregate is determined by computation of the energies of single atoms of that species in bulk and surface environments.

  13. Reversible phosphorylation and regulation of mammalian oocyte meiotic chromatin remodeling and segregation.

    Science.gov (United States)

    Swain, J E; Smith, G D

    2007-01-01

    The mammalian oocyte is notorious for high rates of chromosomal abnormalities. This results in subsequent embryonic aneuploidy, resulting in infertility and congenital defects. Therefore, understanding regulatory mechanisms involved in chromatin remodeling and chromosome segregation during oocyte meiotic maturation is imperative to fully understand the complex process and establish potential therapies. This review will focus on major events occurring during oocyte meiosis, critical to ensure proper cellular ploidy. Mechanistic and cellular events such as chromosome condensation, meiotic spindle formation, as well as cohesion of homologues and sister chromatids will be discussed, focusing on the role of reversible phosphorylation in control of these processes.

  14. Holocentric chromosomes: convergent evolution, meiotic adaptations, and genomic analysis.

    Science.gov (United States)

    Melters, Daniël P; Paliulis, Leocadia V; Korf, Ian F; Chan, Simon W L

    2012-07-01

    In most eukaryotes, the kinetochore protein complex assembles at a single locus termed the centromere to attach chromosomes to spindle microtubules. Holocentric chromosomes have the unusual property of attaching to spindle microtubules along their entire length. Our mechanistic understanding of holocentric chromosome function is derived largely from studies in the nematode Caenorhabditis elegans, but holocentric chromosomes are found over a broad range of animal and plant species. In this review, we describe how holocentricity may be identified through cytological and molecular methods. By surveying the diversity of organisms with holocentric chromosomes, we estimate that the trait has arisen at least 13 independent times (four times in plants and at least nine times in animals). Holocentric chromosomes have inherent problems in meiosis because bivalents can attach to spindles in a random fashion. Interestingly, there are several solutions that have evolved to allow accurate meiotic segregation of holocentric chromosomes. Lastly, we describe how extensive genome sequencing and experiments in nonmodel organisms may allow holocentric chromosomes to shed light on general principles of chromosome segregation.

  15. A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition

    Directory of Open Access Journals (Sweden)

    Kuan-Chung Su

    2016-11-01

    Full Text Available To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosome dynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation.

  16. Entropy-driven spatial organization of highly confined polymers: Lessons for the bacterial chromosome

    Science.gov (United States)

    Jun, Suckjoon; Mulder, Bela

    2006-08-01

    Despite recent progress in visualization experiments, the mechanism underlying chromosome segregation in bacteria still remains elusive. Here we address a basic physical issue associated with bacterial chromosome segregation, namely the spatial organization of highly confined, self-avoiding polymers (of nontrivial topology) in a rod-shaped cell-like geometry. Through computer simulations, we present evidence that, under strong confinement conditions, topologically distinct domains of a polymer complex effectively repel each other to maximize their conformational entropy, suggesting that duplicated circular chromosomes could partition spontaneously. This mechanism not only is able to account for the spatial separation per se but also captures the major features of the spatiotemporal organization of the duplicating chromosomes observed in Escherichia coli and Caulobacter crescentus. bacterial chromosome segregation | Caulobacter crescentus | Escherichia coli | polymer physics

  17. Micronucleus formation causes perpetual unilateral chromosome inheritance in mouse embryos.

    Science.gov (United States)

    Vázquez-Diez, Cayetana; Yamagata, Kazuo; Trivedi, Shardul; Haverfield, Jenna; FitzHarris, Greg

    2016-01-19

    Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.

  18. Grain Boundary Segregation in Metals

    CERN Document Server

    Lejcek, Pavel

    2010-01-01

    Grain boundaries are important structural components of polycrystalline materials used in the vast majority of technical applications. Because grain boundaries form a continuous network throughout such materials, their properties may limit their practical use. One of the serious phenomena which evoke these limitations is the grain boundary segregation of impurities. It results in the loss of grain boundary cohesion and consequently, in brittle fracture of the materials. The current book deals with fundamentals of grain boundary segregation in metallic materials and its relationship to the grain boundary structure, classification and other materials properties.

  19. Bacterial DNA segregation by dynamic SopA polymers

    OpenAIRE

    2005-01-01

    Many bacterial plasmids and chromosomes rely on ParA ATPases for proper positioning within the cell and for efficient segregation to daughter cells. Here we demonstrate that the F-plasmid-partitioning protein SopA polymerizes into filaments in an ATP-dependent manner in vitro, and that the filaments elongate at a rate that is similar to that of plasmid separation in vivo. We show that SopA is a dynamic protein within the cell, undergoing cycles of polymerization and depolymerization, and shut...

  20. Tailings philosophies : to segregate or not to segregate

    Energy Technology Data Exchange (ETDEWEB)

    Wells, P.S. [Suncor Energy, Fort McMurray, AB (Canada)

    2010-07-01

    Traditional technologies for treating oil sands tailings include the segregation of of tailings when discharged into water-filled ponds. The coarser tailings form long beaches. However, the percentage of silts and clays that remain suspended within the water column pose significant challenges to oil sands operators, and contribute to water losses and increases in storage volume. This paper discussed new technologies developed to identify the tailings materials that contribute to the problem and methods designed to isolate and treat the materials. Treatment material balances, process water balances, and material handling requirements for the technologies were evaluated and compared. Three scenarios were considered: (1) a sub-aqueous beaching scenario where tailings were produced by extraction and pumped to a beach storage area for dewatering through self-drainage; (2) a non-segregated tailings (NST) scenario that used mature fine tailings (MFT) drying; (3) and a segregated stream scenario where MFT drying was used where tailings were deposited in traditional tailings ponds. Results of the study showed that the segregated stream tailings treatment system was preferred to NST treatment system. Options for sub-aerial NST deposition may overcome the volume discrepancies between treating fines as well as the required volumes of coarser materials. 5 refs., 2 tabs., 2 figs.

  1. Chromosome Analysis

    Science.gov (United States)

    1998-01-01

    Perceptive Scientific Instruments, Inc., provides the foundation for the Powergene line of chromosome analysis and molecular genetic instrumentation. This product employs image processing technology from NASA's Jet Propulsion Laboratory and image enhancement techniques from Johnson Space Center. Originally developed to send pictures back to earth from space probes, digital imaging techniques have been developed and refined for use in a variety of medical applications, including diagnosis of disease.

  2. Dispensability of the SAC Depends on the Time Window Required by Aurora B to Ensure Chromosome Biorientation

    Science.gov (United States)

    Monje-Casas, Fernando

    2015-01-01

    Aurora B and the spindle assembly checkpoint (SAC) collaborate to ensure the proper biorientation of chromosomes during mitosis. However, lack of Aurora B activity and inactivation of the SAC have a very different impact on chromosome segregation. This is most evident in Saccharomyces cerevisiae, since in this organism the lack of Aurora B is lethal and leads to severe aneuploidy problems, while the SAC is dispensable under normal growth conditions and mutants in this checkpoint do not show evident chromosome segregation defects. We demonstrate that the efficient repair of incorrect chromosome attachments by Aurora B during the initial stages of spindle assembly in budding yeast determines the lack of chromosome segregation defects in SAC mutants, and propose that the differential time window that Aurora B kinase requires to establish chromosome biorientation is the key factor that determines why some cells are more dependent on a functional SAC than others. PMID:26661752

  3. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

  4. Bacillus subtilis chromosome organization oscillates between two distinct patterns.

    Science.gov (United States)

    Wang, Xindan; Montero Llopis, Paula; Rudner, David Z

    2014-09-02

    Bacterial chromosomes have been found to possess one of two distinct patterns of spatial organization. In the first, called "ori-ter" and exemplified by Caulobacter crescentus, the chromosome arms lie side-by-side, with the replication origin and terminus at opposite cell poles. In the second, observed in slow-growing Escherichia coli ("left-ori-right"), the two chromosome arms reside in separate cell halves, on either side of a centrally located origin. These two patterns, rotated 90° relative to each other, appear to result from different segregation mechanisms. Here, we show that the Bacillus subtilis chromosome alternates between them. For most of the cell cycle, newly replicated origins are maintained at opposite poles with chromosome arms adjacent to each other, in an ori-ter configuration. Shortly after replication initiation, the duplicated origins move as a unit to midcell and the two unreplicated arms resolve into opposite cell halves, generating a left-ori-right pattern. The origins are then actively segregated toward opposite poles, resetting the cycle. Our data suggest that the condensin complex and the parABS partitioning system are the principal driving forces underlying this oscillatory cycle. We propose that the distinct organization patterns observed for bacterial chromosomes reflect a common organization-segregation mechanism, and that simple modifications to it underlie the unique patterns observed in different species.

  5. Cell division control by the Chromosomal Passenger Complex

    Energy Technology Data Exchange (ETDEWEB)

    Waal, Maike S. van der; Hengeveld, Rutger C.C.; Horst, Armando van der; Lens, Susanne M.A., E-mail: s.m.a.lens@umcutrecht.nl

    2012-07-15

    The Chromosomal Passenger Complex (CPC) consisting of Aurora B kinase, INCENP, Survivin and Borealin, is essential for genomic stability by controlling multiple processes during both nuclear and cytoplasmic division. In mitosis it ensures accurate segregation of the duplicated chromosomes by regulating the mitotic checkpoint, destabilizing incorrectly attached spindle microtubules and by promoting the axial shortening of chromosomal arms in anaphase. During cytokinesis the CPC most likely prevents chromosome damage by imposing an abscission delay when a chromosome bridge connects the two daughter cells. Moreover, by controlling proper cytoplasmic division, the CPC averts tetraploidization. This review describes recent insights on how the CPC is capable of conducting its various functions in the dividing cell to ensure chromosomal stability.

  6. The role of BUBR1 in the maintenance of chromosomal stability

    NARCIS (Netherlands)

    Suijkerbuijk, S.J.E.

    2012-01-01

    The majority of solid tumours contain an incorrect number of chromosomes. This state, called aneuploidy, can be caused by defects in chromosome segregation during the division of cells. Prevention against aneuploidy is dependent on BUBR1. This protein is an essential component of a surveillance mech

  7. A role for Aurora C in the chromosomal passenger complex during human preimplantation embryo development

    NARCIS (Netherlands)

    Santos, Margarida Avo; van de Werken, Christine; de Vries, Marieke; Jahr, Holger; Vromans, Martijn J. M.; Laven, Joop S. E.; Fauser, Bart C.; Kops, Geert J.; Lens, Susanne M.; Baart, Esther B.

    2011-01-01

    BACKGROUND: Human embryos generated by IVF demonstrate a high incidence of chromosomal segregation errors during the cleavage divisions. To analyse underlying molecular mechanisms, we investigated the behaviour of the chromosomal passenger complex (CPC) in human oocytes and embryos. This important m

  8. The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex chromosome and meiotic mechanism evolution.

    Science.gov (United States)

    Blackmon, Heath; Demuth, Jeffery P

    2015-09-01

    Loss of the Y-chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y-chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y-chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose positive selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y-chromosome aneuploidy raise doubt about the prospects for long-term retention of the human Y-chromosome despite recent evidence for stable gene content in older non-recombining regions.

  9. Chromatids segregate without centrosomes during Caenorhabditis elegans mitosis in a Ran- and CLASP-dependent manner.

    Science.gov (United States)

    Nahaboo, Wallis; Zouak, Melissa; Askjaer, Peter; Delattre, Marie

    2015-06-01

    During mitosis, chromosomes are connected to a microtubule-based spindle. Current models propose that displacement of the spindle poles and/or the activity of kinetochore microtubules generate mechanical forces that segregate sister chromatids. Using laser destruction of the centrosomes during Caenorhabditis elegans mitosis, we show that neither of these mechanisms is necessary to achieve proper chromatid segregation. Our results strongly suggest that an outward force generated by the spindle midzone, independently of centrosomes, is sufficient to segregate chromosomes in mitotic cells. Using mutant and RNAi analysis, we show that the microtubule-bundling protein SPD-1/MAP-65 and BMK-1/kinesin-5 act as a brake opposing the force generated by the spindle midzone. Conversely, we identify a novel role for two microtubule-growth and nucleation agents, Ran and CLASP, in the establishment of the centrosome-independent force during anaphase. Their involvement raises the interesting possibility that microtubule polymerization of midzone microtubules is continuously required to sustain chromosome segregation during mitosis.

  10. Meiotic pairing of B chromosomes, multiple sexual system, and Robertsonian fusion in the red brocket deer Mazama americana (Mammalia, Cervidae).

    Science.gov (United States)

    Aquino, C I; Abril, V V; Duarte, J M B

    2013-09-13

    Deer species of the genus Mazama show significant inter- and intraspecific chromosomal variation due to the occurrence of rearrangements and B chromosomes. Given that carriers of aneuploidies and structural rearrangements often show anomalous chromosome pairings, we here performed a synaptonemal complex analysis to study chromosome pairing behavior in a red brocket deer (Mazama americana) individual that is heterozygous for a Robertsonian translocation, is a B chromosome carrier, and has a multiple sex chromosome system (XY₁Y₂). The synaptonemal complex in spermatocytes showed normal chromosome pairings for all chromosomes, including the autosomal and sex trivalents. The electromicrographs showed homology among B chromosomes since they formed bivalents, but they also appeared as univalents, indicating their anomalous behavior and non-Mendelian segregation. Thus, synaptonemal complex analysis is a useful tool to evaluate the role of B chromosomes and rearrangements during meiosis on the intraspecific chromosomal variation that is observed in the majority of Mazama species.

  11. Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis.

    Science.gov (United States)

    Gascoigne, Karen E; Cheeseman, Iain M

    2013-07-01

    Chromosomal rearrangements can radically alter gene products and their function, driving tumor formation or progression. However, the molecular origins and evolution of such rearrangements are varied and poorly understood, with cancer cells often containing multiple, complex rearrangements. One mechanism that can lead to genomic rearrangements is the formation of a "dicentric" chromosome containing two functional centromeres. Indeed, such dicentric chromosomes have been observed in cancer cells. Here, we tested the ability of a single dicentric chromosome to contribute to genomic instability and neoplastic conversion in vertebrate cells. We developed a system to transiently and reversibly induce dicentric chromosome formation on a single chromosome with high temporal control. We find that induced dicentric chromosomes are frequently damaged and mis-segregated during mitosis, and that this leads to extensive chromosomal rearrangements including translocations with other chromosomes. Populations of pre-neoplastic cells in which a single dicentric chromosome is induced acquire extensive genomic instability and display hallmarks of cellular transformation including anchorage-independent growth in soft agar. Our results suggest that a single dicentric chromosome could contribute to tumor initiation.

  12. International perspectives on countering school segregation

    NARCIS (Netherlands)

    Bakker, J.T.A.; Denessen, E.J.P.G.; Peters, T.J.M.; Walraven, G.

    2010-01-01

    School segregation is perceived as an unyielding problem worldwide, which is manifest along both ethnic and socio-economic lines. With this edited volume we aim to share information about school segregation and policies focused on countering school segregation from an international perspective. Many

  13. Centrosome dynamics as a source of chromosomal instability

    NARCIS (Netherlands)

    Nam, H.J.; Naylor, R.M.; Deursen, J.M.A. van

    2015-01-01

    Accurate segregation of duplicated chromosomes between two daughter cells depends on bipolar spindle formation, a metaphase state in which sister kinetochores are attached to microtubules emanating from opposite spindle poles. To ensure bi-orientation, cells possess surveillance systems that safegua

  14. Roles of cohesin and condensin in chromosome dynamics during mammalian meiosis.

    Science.gov (United States)

    Lee, Jibak

    2013-10-01

    Meiosis is a key step for sexual reproduction in which chromosome number is halved by two successive meiotic divisions after a single round of DNA replication. In the first meiotic division (meiosis I), homologous chromosomes pair, synapse, and recombine with their partners in prophase I. As a result, homologous chromosomes are physically connected until metaphase I and then segregated from each other at the onset of anaphase I. In the subsequent second meiotic division (meiosis II), sister chromatids are segregated. Chromosomal abnormality arising during meiosis is one of the major causes of birth defects and congenital disorders in mammals including human and domestic animals. Hence understanding of the mechanism underlying these unique chromosome behavior in meiosis is of great importance. This review focuses on the roles of cohesin and condensin, and their regulation in chromosome dynamics during mammalian meiosis.

  15. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes.

    Science.gov (United States)

    Thayer, Mathew J

    2012-09-01

    Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.

  16. Meiotic segregation and interchromosomal effect in the sperm of a double translocation carrier: a case report

    Directory of Open Access Journals (Sweden)

    Laureano Lucimar AF

    2009-12-01

    Full Text Available Abstract Background Infertility is a natural mechanism of selection intended to prevent the delivery of a child with malformations or mental retardation. Male infertility is closely related to chromosomal abnormalities. This study was focused on the analysis of meiotic segregation involving a Robertsonian translocation, 45,XY,der(13;13 [56]/45,XY,der(13;14 [44] and the evaluation of possible interchromosomal effects. Results Hybridisation with LSI 13q14 and subtelomere 14q probes and WCP13 SpectrumGreen and WCP14 SpectrumOrange probes showed a high proportion of unbalanced gametes, corresponding to 71.2% of the spermatozoa. The disomic frequencies of the sexual chromosomes and chromosome 18 of the patient were higher (5.28% and 2.55%, respectively than those of the control (0.6% and 0.59%, respectively. Conclusion Meiotic segregation studies in sperm are an important tool for genetic counselling of chromosomal aberrations, allowing for a prediction of the risks and consequent implications for the reproductive life. The patient with this rare translocation exhibited meiotic segregation fidelity, and a high rate of unbalanced gametes with disomic spermatozoa.

  17. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

    Directory of Open Access Journals (Sweden)

    Maia André F

    2008-05-01

    Full Text Available Abstract During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension. In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this.

  18. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond.

    Science.gov (United States)

    Vader, Gerben; Maia, André F; Lens, Susanne Ma

    2008-05-28

    During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension). In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this.

  19. Uniparental disomy analysis in carriers of balanced chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    May, K.M.; Pettay, D.; Muralidharan, K. [Emory Univ. School of Medicine, Atlanta, GA (United States)] [and others

    1994-09-01

    Although most individuals who carry a balanced familial chromosome rearrangement are phenotypically normal, those who are clinically abnormal raise the question of whether or not the rearrangement plays a causative role. One possible mechanism involves meiotic segregation of a normal homolog along with the rearranged chromosome(s) such that a trisomic conception occurs. Subsequent loss by mitotic nondisjunction of the structurally normal chromosome contributed by the non-carrier parent would then result in uniparental disomy (UPD) in a conceptus carrying a balanced rearrangement. UPD for chromosomes 14 and 15 has been demonstrated in several clinically abnormal individuals who carry a familial Robertsonian translocation. We have extended this type of analysis to include other forms of balanced chromosome rearrangements. We report the results of UPD analysis of 14 families who have a phenotypically abnormal child with an apparently balanced rearrangement. The series includes 4 reciprocal translocations, 4 Robertsonian translocations, 2 X;autosome translocations, and 4 inversions. High resolution chromosomes were used to compare breakpoints between parent and offspring to exclude the possibility of further rearrangements. Parental origin of the chromosome(s) involved was determined by DNA polymorphism analysis using PCR or Southern blotting techniques. We found no evidence of UPD in any of the 14 cases. Our data suggest that UPD is not a common explanation for phenotypically abnormal carriers of balanced chromosome rearrangements.

  20. The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly.

    Science.gov (United States)

    Magidson, Valentin; O'Connell, Christopher B; Lončarek, Jadranka; Paul, Raja; Mogilner, Alex; Khodjakov, Alexey

    2011-08-19

    Error-free chromosome segregation requires stable attachment of sister kinetochores to the opposite spindle poles (amphitelic attachment). Exactly how amphitelic attachments are achieved during spindle assembly remains elusive. We employed photoactivatable GFP and high-resolution live-cell confocal microscopy to visualize complete 3D movements of individual kinetochores throughout mitosis in nontransformed human cells. Combined with electron microscopy, molecular perturbations, and immunofluorescence analyses, this approach reveals unexpected details of chromosome behavior. Our data demonstrate that unstable lateral interactions between kinetochores and microtubules dominate during early prometaphase. These transient interactions lead to the reproducible arrangement of chromosomes in an equatorial ring on the surface of the nascent spindle. A computational model predicts that this toroidal distribution of chromosomes exposes kinetochores to a high density of microtubules which facilitates subsequent formation of amphitelic attachments. Thus, spindle formation involves a previously overlooked stage of chromosome prepositioning which promotes formation of amphitelic attachments.

  1. Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes.

    Science.gov (United States)

    Kitajima, Tomoya S; Ohsugi, Miho; Ellenberg, Jan

    2011-08-19

    Chromosomes must establish stable biorientation prior to anaphase to achieve faithful segregation during cell division. The detailed process by which chromosomes are bioriented and how biorientation is coordinated with spindle assembly and chromosome congression remain unclear. Here, we provide complete 3D kinetochore-tracking datasets throughout cell division by high-resolution imaging of meiosis I in live mouse oocytes. We show that in acentrosomal oocytes, chromosome congression forms an intermediate chromosome configuration, the prometaphase belt, which precedes biorientation. Chromosomes then invade the elongating spindle center to form the metaphase plate and start biorienting. Close to 90% of all chromosomes undergo one or more rounds of error correction of their kinetochore-microtubule attachments before achieving correct biorientation. This process depends on Aurora kinase activity. Our analysis reveals the error-prone nature of homologous chromosome biorientation, providing a possible explanation for the high incidence of aneuploid eggs observed in mammals, including humans.

  2. Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes.

    Science.gov (United States)

    Schvarzstein, Mara; Wignall, Sarah M; Villeneuve, Anne M

    2010-02-01

    Organisms that reproduce sexually must reduce their chromosome number by half during meiosis to generate haploid gametes. To achieve this reduction in ploidy, organisms must devise strategies to couple sister chromatids so that they stay together during the first meiotic division (when homologous chromosomes separate) and then segregate away from one another during the second division. Here we review recent findings that shed light on how Caenorhabditis elegans, an organism with holocentric chromosomes, deals with these challenges of meiosis by differentiating distinct chromosomal subdomains and remodeling chromosome structure during prophase. Furthermore, we discuss how features of chromosome organization established during prophase affect later chromosome behavior during the meiotic divisions. Finally, we illustrate how analysis of holocentric meiosis can inform our thinking about mechanisms that operate on monocentric chromosomes.

  3. Feedback control of chromosome separation by a midzone Aurora B gradient

    Science.gov (United States)

    Pereira, António J.; Aguiar, Paulo; Lampson, Michael A.; Maiato, Helder

    2017-01-01

    Accurate chromosome segregation during mitosis requires the physical separation of sister chromatids before nuclear envelope reassembly (NER). However, how these two processes are coordinated remains unknown. Here, we identified a conserved feedback control mechanism that delays chromosome decondensation and NER in response to incomplete chromosome separation during anaphase. A midzone-associated Aurora B gradient was found to monitor chromosome position along the division axis and to prevent premature chromosome decondensation by retaining Condensin I. PP1/PP2A phosphatases counteracted this gradient and promoted chromosome decondensation and NER. Thus, an Aurora B gradient appears to mediate a surveillance mechanism that prevents chromosome decondensation and NER until effective separation of sister chromatids is achieved. This allows the correction and reintegration of lagging chromosomes in the main nuclei before completion of NER. PMID:24925910

  4. Sexual segregation in foraging giraffe

    Science.gov (United States)

    Mramba, Rosemary Peter; Mahenya, Obeid; Siyaya, Annetjie; Mathisen, Karen Marie; Andreassen, Harry Peter; Skarpe, Christina

    2017-02-01

    Sexual segregation in giraffe is known to vary between savannas. In this study, we compared sexual segregation in giraffe in one nutrient-rich savanna, the Serengeti National Park, one nutrient-poor, Mikumi National Park, and one medium rich savanna, Arusha National Park, (from here on referred to just by name) based on effects of sexual size dimorphism and related hypotheses. Data were collected in the wet and dry seasons, by driving road transects and making visual observations of browsing giraffe. Additional data were collected from literature (plant chemistry; mammal communities). There was a noticeable difference in browsing by females and males and in browsing between the three savannas. Females browsed a higher diversity of tree species in Serengeti whereas males browsed a higher diversity in Arusha, while the diversity of species browsed in Mikumi was high and about the same in both sexes. Females selected for high concentrations of nitrogen and low concentrations of tannins and phenolics compared to males in Serengeti but selection in Mikumi was more complex. Males browsed higher in the canopy than females in all sites, but the browsing height was generally higher in Serengeti than Mikumi and Arusha. Season had an effect on the browsing height independent of sex in Mikumi, where giraffes browsed higher in the dry season compared to the wet season. Males spent more time browsing per tree compared to females in all three sites; however, browsing time in Mikumi was also affected by season, where giraffes had longer browsing bouts in the wet season compared to the dry season. We suggest that sexual differences in forage requirement and in foraging interacts with differences in tree chemistry and in competing herbivore communities between nutrient rich and nutrient poor savanna in shaping the sexual segregation.

  5. Centromere inactivation on a neo-Y fusion chromosome in threespine stickleback fish.

    Science.gov (United States)

    Cech, Jennifer N; Peichel, Catherine L

    2016-12-01

    Having one and only one centromere per chromosome is essential for proper chromosome segregation during both mitosis and meiosis. Chromosomes containing two centromeres are known as dicentric and often mis-segregate during cell division, resulting in aneuploidy or chromosome breakage. Dicentric chromosome can be stabilized by centromere inactivation, a process which reestablishes monocentric chromosomes. However, little is known about this process in naturally occurring dicentric chromosomes. Using a combination of fluorescence in situ hybridization (FISH) and immunofluorescence combined with FISH (IF-FISH) on metaphase chromosome spreads, we demonstrate that centromere inactivation has evolved on a neo-Y chromosome fusion in the Japan Sea threespine stickleback fish (Gasterosteus nipponicus). We found that the centromere derived from the ancestral Y chromosome has been inactivated. Our data further suggest that there have been genetic changes to this centromere in the two million years since the formation of the neo-Y chromosome, but it remains unclear whether these genetic changes are a cause or consequence of centromere inactivation.

  6. ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15.

    Directory of Open Access Journals (Sweden)

    Nathan Donley

    2015-01-01

    Full Text Available DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this locus identified long, RNA transcripts that are retained in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found that this locus displays asynchronous replication that is coordinated with other random monoallelic genes on chromosome 15. We have named this locus ASynchronous replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed mitotic condensation and structural instability of human chromosome 6. Previous studies in the mouse found that deletion of the Xist gene, from the X chromosome in adult somatic cells, results in a delayed replication and instability phenotype that is indistinguishable from the phenotype caused by disruption of either ASAR6 or ASAR15. In addition, delayed replication and chromosome instability were detected following structural rearrangement of many different human or mouse chromosomes. These observations suggest that all mammalian chromosomes contain similar cis-acting loci. Thus, under this scenario, all mammalian chromosomes contain four distinct types of essential cis-acting elements: origins, telomeres, centromeres and "inactivation/stability centers", all functioning to promote proper replication, segregation and structural stability of each chromosome.

  7. Filament depolymerization can explain chromosome pulling during bacterial mitosis.

    Science.gov (United States)

    Banigan, Edward J; Gelbart, Michael A; Gitai, Zemer; Wingreen, Ned S; Liu, Andrea J

    2011-09-01

    Chromosome segregation is fundamental to all cells, but the force-generating mechanisms underlying chromosome translocation in bacteria remain mysterious. Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA protein structure elongates from the new cell pole, binds to a ParB-decorated chromosome, and then retracts via disassembly, pulling the chromosome across the cell. This poses the question of how a depolymerizing structure can robustly pull the chromosome that disassembles it. We perform Brownian dynamics simulations with a simple, physically consistent model of the ParABS system. The simulations suggest that the mechanism of translocation is "self-diffusiophoretic": by disassembling ParA, ParB generates a ParA concentration gradient so that the ParA concentration is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the ParA gradient and across the cell. We find that translocation is most robust when ParB binds side-on to ParA filaments. In this case, robust translocation occurs over a wide parameter range and is controlled by a single dimensionless quantity: the product of the rate of ParA disassembly and a characteristic relaxation time of the chromosome. This time scale measures the time it takes for the chromosome to recover its average shape after it is has been pulled. Our results suggest explanations for observed phenomena such as segregation failure, filament-length-dependent translocation velocity, and chromosomal compaction.

  8. Filament depolymerization can explain chromosome pulling during bacterial mitosis.

    Directory of Open Access Journals (Sweden)

    Edward J Banigan

    2011-09-01

    Full Text Available Chromosome segregation is fundamental to all cells, but the force-generating mechanisms underlying chromosome translocation in bacteria remain mysterious. Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA protein structure elongates from the new cell pole, binds to a ParB-decorated chromosome, and then retracts via disassembly, pulling the chromosome across the cell. This poses the question of how a depolymerizing structure can robustly pull the chromosome that disassembles it. We perform Brownian dynamics simulations with a simple, physically consistent model of the ParABS system. The simulations suggest that the mechanism of translocation is "self-diffusiophoretic": by disassembling ParA, ParB generates a ParA concentration gradient so that the ParA concentration is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the ParA gradient and across the cell. We find that translocation is most robust when ParB binds side-on to ParA filaments. In this case, robust translocation occurs over a wide parameter range and is controlled by a single dimensionless quantity: the product of the rate of ParA disassembly and a characteristic relaxation time of the chromosome. This time scale measures the time it takes for the chromosome to recover its average shape after it is has been pulled. Our results suggest explanations for observed phenomena such as segregation failure, filament-length-dependent translocation velocity, and chromosomal compaction.

  9. Identification of All Genotypes in Tetraploid Ryegrass (Lolium spp.) Segregating for Four Alleles in a Pgi-Enzyme Locus

    DEFF Research Database (Denmark)

    Nielsen, Gunnar Gissel

    1980-01-01

    A phosphoglucoisomerase locus (Pgi-2) segregates for four alleles in chromosome-doubled plants of the two ryegrasses, Lolium perenne and L. multiflorum. After separation by starch gel electrophoresis, all the possible 35 genotypes have been identified by means of the gene dosage effect on the iso...

  10. Perceptual-binding and persistent surface segregation

    OpenAIRE

    2004-01-01

    Visual input is segregated in the brain into subsystems that process different attributes such as motion and color. At the same time, visual information is perceptually segregated into objects and surfaces. Here we demonstrate that perceptual segregation of visual entities based on a transparency cue precedes and affects perceptual binding of attributes. Adding an irrelevant transparency cue paradoxically improved the pairing of color and motion for rapidly alternating surfaces. Subsequent ex...

  11. Chromosomal mapping of the structural gene coding for the mouse cell adhesion molecule uvomorulin

    Energy Technology Data Exchange (ETDEWEB)

    Eistetter, H.R.; Adolph, S.; Ringwald, M.; Simon-Chazottes, D.; Schuh, R.; Guenet, J.L.; Kemler, R. (Max-Planck-Gesellschaft, Tuebingen (West Germany))

    1988-05-01

    The gene coding for the mouse cell adhesion molecule uvomorulin has been mapped to chromosome 8. Uvomorulin cDNA clone F5H3 identified restriction fragment length polymorphisms in Southern blots of genomic DNA from mouse species Mus musculus domesticus and Mus spretus. By analyzing the segregation pattern of the gene in 75 offspring from an interspecific backcross a single genetic locus, Um, was defined on chromosome 8. Recombination frequency between Um and the co-segregating loci serum esterase 1 (Es-1) and tyrosine aminotransferase (Tat) places Um about 14 centimorgan (cM) distal to Es-1, and 5 cM proximal to Tat. In situ hybridization of uvomorulin ({sup 3}H)cDNA to mouse metaphase chromosomes located the Um locus close to the distal end of chromosome 8 (bands C3-E1). Since uvomorulin is evolutionarily highly conserved, its chromosomal assignment adds an important marker to the mouse genetic map.

  12. From particle segregation to the granular clock

    Energy Technology Data Exchange (ETDEWEB)

    Lambiotte, R. [Physique Statistique, Plasmas et Optique Non-lineaire, Universite Libre de Bruxelles, Campus Plaine, Boulevard du Triomphe, Code Postal 231, 1050 Brussels (Belgium)]. E-mail: rlambiot@ulb.ac.be; Salazar, J.M. [Universite De Bougogne-LRRS UMR-5613 CNRS, Faculte des Sciences Mirande, 9 Av. Alain Savary, 21078 Dijon Cedex (France)]. E-mail: jmarcos@u-bourgogne.fr; Brenig, L. [Physique Statistique, Plasmas et Optique Non-lineaire, Universite Libre de Bruxelles, Campus Plaine, Boulevard du Triomphe, Code Postal 231, 1050 Brussels (Belgium)]. E-mail: lbrenig@ulb.ac.be

    2005-08-01

    Recently several authors studied the segregation of particles for a system composed of mono-dispersed inelastic spheres contained in a box divided by a wall in the middle. The system exhibited a symmetry breaking leading to an overpopulation of particles in one side of the box. Here we study the segregation of a mixture of particles composed of inelastic hard spheres and fluidized by a vibrating wall. Our numerical simulations show a rich phenomenology: horizontal segregation and periodic behavior. We also propose an empirical system of ODEs representing the proportion of each type of particles and the segregation flux of particles. These equations reproduce the major features observed by the simulations.

  13. Perceptual-binding and persistent surface segregation.

    Science.gov (United States)

    Moradi, Farshad; Shimojo, Shinsuke

    2004-11-01

    Visual input is segregated in the brain into subsystems that process different attributes such as motion and color. At the same time, visual information is perceptually segregated into objects and surfaces. Here we demonstrate that perceptual segregation of visual entities based on a transparency cue precedes and affects perceptual binding of attributes. Adding an irrelevant transparency cue paradoxically improved the pairing of color and motion for rapidly alternating surfaces. Subsequent experiments show: (1) Attributes are registered over the temporal window defined by the perceptual persistence of segregation, resulting in asynchrony in binding, and (2) attention is necessary for correct registration of attributes in the presence of ambiguity.

  14. The Smc5-Smc6 complex is required to remove chromosome junctions in meiosis.

    Directory of Open Access Journals (Sweden)

    Sarah Farmer

    Full Text Available Meiosis, a specialized cell division with a single cycle of DNA replication round and two consecutive rounds of nuclear segregation, allows for the exchange of genetic material between parental chromosomes and the formation of haploid gametes. The structural maintenance of chromosome (SMC proteins aid manipulation of chromosome structures inside cells. Eukaryotic SMC complexes include cohesin, condensin and the Smc5-Smc6 complex. Meiotic roles have been discovered for cohesin and condensin. However, although Smc5-Smc6 is known to be required for successful meiotic divisions, the meiotic functions of the complex are not well understood. Here we show that the Smc5-Smc6 complex localizes to specific chromosome regions during meiotic prophase I. We report that meiotic cells lacking Smc5-Smc6 undergo catastrophic meiotic divisions as a consequence of unresolved linkages between chromosomes. Surprisingly, meiotic segregation defects are not rescued by abrogation of Spo11-induced meiotic recombination, indicating that at least some chromosome linkages in smc5-smc6 mutants originate from other cellular processes. These results demonstrate that, as in mitosis, Smc5-Smc6 is required to ensure proper chromosome segregation during meiosis by preventing aberrant recombination intermediates between homologous chromosomes.

  15. Genetic architecture of male sterility and segregation distortion in Drosophila pseudoobscura Bogota-USA hybrids.

    Science.gov (United States)

    Phadnis, Nitin

    2011-11-01

    Understanding the genetic basis of reproductive isolation between recently diverged species is a central problem in evolutionary genetics. Here, I present analyses of the genetic architecture underlying hybrid male sterility and segregation distortion between the Bogota and USA subspecies of Drosophila pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be necessary but not sufficient for both male sterility and segregation distortion in F(1) hybrids between these subspecies, requiring several interacting partner loci for full manifestation of hybrid phenomena. I map these partner loci separately on the Bogota X chromosome and USA autosomes using a combination of different mapping strategies. I find that hybrid sterility involves a single hybrid incompatibility of at least seven interacting partner genes that includes three large-effect loci. Segregation distortion involves three loci on the Bogota X chromosome and one locus on the autosomes. The genetic bases of hybrid sterility and segregation distortion are at least partially--but not completely--overlapping. My results lay the foundation for fine-mapping experiments to identify the complete set of genes that interact with Overdrive. While individual genes that cause hybrid sterility or inviability have been identified in a few cases, my analysis provides a comprehensive look at the genetic architecture of all components of a hybrid incompatibility underlying F(1) hybrid sterility. Such an analysis would likely be unfeasible for most species pairs due to their divergence time and emphasizes the importance of young species pairs such as the D. pseudoobscura subspecies studied here.

  16. Dicentric chromosomes: unique models to study centromere function and inactivation.

    Science.gov (United States)

    Stimpson, Kaitlin M; Matheny, Justyne E; Sullivan, Beth A

    2012-07-01

    Dicentric chromosomes are products of genome rearrangement that place two centromeres on the same chromosome. Depending on the organism, dicentric stability varies after formation. In humans, dicentrics occur naturally in a substantial portion of the population and usually segregate successfully in mitosis and meiosis. Their stability has been attributed to inactivation of one of the two centromeres, creating a functionally monocentric chromosome that can segregate normally during cell division. The molecular basis for centromere inactivation is not well understood, although studies in model organisms and in humans suggest that genomic and epigenetic mechanisms can be involved. Furthermore, constitutional dicentric chromosomes ascertained in patients presumably represent the most stable chromosomes, so the spectrum of dicentric fates, if it exists, is not entirely clear. Studies of engineered or induced dicentrics in budding yeast and plants have provided significant insight into the fate of dicentric chromosomes. And, more recently, studies have shown that dicentrics in humans can also undergo multiple fates after formation. Here, we discuss current experimental evidence from various organisms that has deepened our understanding of dicentric behavior and the intriguingly complex process of centromere inactivation.

  17. Lack of response to unaligned chromosomes in mammalian female gametes.

    Science.gov (United States)

    Sebestova, Jaroslava; Danylevska, Anna; Novakova, Lucia; Kubelka, Michal; Anger, Martin

    2012-08-15

    Chromosome segregation errors are highly frequent in mammalian female meiosis, and their incidence gradually increases with maternal age. The fate of aneuploid eggs is obviously dependent on the stringency of mechanisms for detecting unattached or repairing incorrectly attached kinetochores. In case of their failure, the newly formed embryo will inherit the impaired set of chromosomes, which will have severe consequences for its further development. Whether spindle assembly checkpoint (SAC) in oocytes is capable of arresting cell cycle progression in response to unaligned kinetochores was discussed for a long time. It is known that abolishing SAC increases frequency of chromosome segregation errors and causes precocious entry into anaphase; SAC, therefore, seems to be essential for normal chromosome segregation in meiosis I. However, it was also reported that for anaphase-promoting complex (APC) activation, which is a prerequisite for entering anaphase; alignment of only a critical mass of kinetochores on equatorial plane is sufficient. This indicates that the function of SAC and of cooperating chromosome attachment correction mechanisms in oocytes is different from somatic cells. To analyze this phenomenon, we used live cell confocal microscopy to monitor chromosome movements, spindle formation, APC activation and polar body extrusion (PBE) simultaneously in individual oocytes at various time points during first meiotic division. Our results, using oocytes from aged animals and interspecific crosses, demonstrate that multiple unaligned kinetochores and severe congression defects are tolerated at the metaphase to anaphase transition, although such cells retain sensitivity to nocodazole. This indicates that checkpoint mechanisms, operating in oocytes at this point, are essential for accurate timing of APC activation in meiosis I, but they are insufficient in detection or correction of unaligned chromosomes, preparing thus conditions for propagation of the aneuploidy

  18. The fate of the mosaic embryo : chromosomal constitution and development of Day 4, 5 and 8 human embryos

    NARCIS (Netherlands)

    Santos, Margarida Avo; Teklenburg, Gijs; Macklon, Nick S.; Van Opstal, Diane; Schuring-Blom, G. Heleen; Krijtenburg, Pieter-Jaap; de Vreeden-Elbertse, Johanna; Fauser, Bart C.; Baart, Esther B.

    2010-01-01

    Post-zygotic chromosome segregation errors are very common in human embryos after in vitro fertilization, resulting in mosaic embryos. However, the significance of mosaicism for the developmental potential of early embryos is unknown. We assessed chromosomal constitution and development of embryos f

  19. The fate of the mosaic embryo: Chromosomal constitution and development of Day 4, 5 and 8 human embryos

    NARCIS (Netherlands)

    M.A. Santos; G. Teklenburg (Gijs); N.S. Macklon (Nick); D. van Opstal (Diane); G.H. Schuring-Blom (Heleen); P-J. Krijtenburg (Pieter-Jaap); J. de Vreeden-Elbertse (Johanna); B.C.J.M. Fauser (Bart); E.B. Baart (Esther)

    2010-01-01

    textabstractBackground: Post-zygotic chromosome segregation errors are very common in human embryos after in vitro fertilization, resulting in mosaic embryos. However, the significance of mosaicism for the developmental potential of early embryos is unknown. We assessed chromosomal constitution and

  20. Decreased H3K27 and H3K4 trimethylation on mortal chromosomes in distributed stem cells.

    Science.gov (United States)

    Huh, Y H; Sherley, J L

    2014-12-04

    The role of immortal DNA strands that co-segregate during mitosis of asymmetrically self-renewing distributed stem cells (DSCs) is unknown. Previously, investigation of immortal DNA strand function and molecular mechanisms responsible for their nonrandom co-segregation was precluded by difficulty in identifying DSCs and immortal DNA strands. Here, we report the use of two technological innovations, selective DSC expansion and establishment of H2A.Z chromosomal asymmetry as a specific marker of 'immortal chromosomes,' to investigate molecular properties of immortal chromosomes and opposing 'mortal chromosomes' in cultured mouse hair follicle DSCs. Although detection of the respective suppressive and activating H3K27me3 and H3K4me3 epigenetic marks on immortal chromosomes was similar to randomly segregated chromosomes, detection of both was lower on mortal chromosomes destined for lineage-committed sister cells. This global epigenomic feature of nonrandom co-segregation may reveal a mechanism that maintains an epigenome-wide 'poised' transcription state, which preserves DSC identity, while simultaneously activating sister chromosomes for differentiation.

  1. Organizing the bacterial chromosome for division

    Science.gov (United States)

    Broedersz, Chase

    2014-03-01

    The chromosome is highly organized in space in many bacteria, although the origin and function of this organization remain unclear. This organization is further complicated by the necessity for chromosome replication and segregation. Partitioning proteins of the ParABS system mediate chromosomal and plasmid segregation in a variety of bacteria. This segregation machinery includes a large ParB-DNA complex consisting of roughly 1000 ParB dimers, which localizes around one or a few centromere-like parS sites near the origin of replication. Despite the apparent simplicity of this segregation machinery as compared to eukaryotic segregations systems, puzzles remain: In particular, what is the nature of interactions among DNA-bound ParB proteins, and how do these determine the organizational and functional properties of the ParB-DNA partitioning complex? A crucial aspect of this question is whether ParB spreads along the DNA to form a filamentous protein-DNA complex with a 1D character, or rather assembles to form a 3D complex on the DNA. Furthermore, it remains unclear how the presence of only one or even a few parS sites can lead to robust formation and localization of such a large protein-DNA complex. We developed a simple model for interacting proteins on DNA, and found that a combination of 1D spreading bonds and a 3D bridging bond between ParB proteins constitutes the minimal model for condensation of a 3D ParB-DNA complex. These combined interactions provide an effective surface tension that prevents fragmentation of the ParB-DNA complex. Thus, ParB spreads to form multiple 1D domains on the DNA, connected in 3D by bridging interactions to assemble into a 3D ParB-DNA condensate. Importantly, this model accounts for recent experiments on ParB-induced gene-silencing and the effect of a DNA ``roadblock'' on ParB localization. Furthermore, our model provides a simple mechanism to explain how a single parS site is both necessary and sufficient for the formation and

  2. Stretching the rules: monocentric chromosomes with multiple centromere domains.

    Science.gov (United States)

    Neumann, Pavel; Navrátilová, Alice; Schroeder-Reiter, Elizabeth; Koblížková, Andrea; Steinbauerová, Veronika; Chocholová, Eva; Novák, Petr; Wanner, Gerhard; Macas, Jiří

    2012-01-01

    The centromere is a functional chromosome domain that is essential for faithful chromosome segregation during cell division and that can be reliably identified by the presence of the centromere-specific histone H3 variant CenH3. In monocentric chromosomes, the centromere is characterized by a single CenH3-containing region within a morphologically distinct primary constriction. This region usually spans up to a few Mbp composed mainly of centromere-specific satellite DNA common to all chromosomes of a given species. In holocentric chromosomes, there is no primary constriction; the centromere is composed of many CenH3 loci distributed along the entire length of a chromosome. Using correlative fluorescence light microscopy and high-resolution electron microscopy, we show that pea (Pisum sativum) chromosomes exhibit remarkably long primary constrictions that contain 3-5 explicit CenH3-containing regions, a novelty in centromere organization. In addition, we estimate that the size of the chromosome segment delimited by two outermost domains varies between 69 Mbp and 107 Mbp, several factors larger than any known centromere length. These domains are almost entirely composed of repetitive DNA sequences belonging to 13 distinct families of satellite DNA and one family of centromeric retrotransposons, all of which are unevenly distributed among pea chromosomes. We present the centromeres of Pisum as novel "meta-polycentric" functional domains. Our results demonstrate that the organization and DNA composition of functional centromere domains can be far more complex than previously thought, do not require single repetitive elements, and do not require single centromere domains in order to segregate properly. Based on these findings, we propose Pisum as a useful model for investigation of centromere architecture and the still poorly understood role of repetitive DNA in centromere evolution, determination, and function.

  3. The two chromosomes of Vibrio cholerae are initiated at different time points in the cell cycle

    DEFF Research Database (Denmark)

    Rasmussen, Tue; Jensen, Rasmus Bugge; Skovgaard, Ole

    2007-01-01

    for analysing flow cytometry data and marker frequency analysis, we show that the small chromosome II is replicated late in the C period of the cell cycle, where most of chromosome I has been replicated. Owing to the delay in initiation of chromosome II, the two chromosomes terminate replication...... at approximately the same time and the average number of replication origins per cell is higher for chromosome I than for chromosome II. Analysis of cell-cycle parameters shows that chromosome replication and segregation is exceptionally fast in V. cholerae. The divided genome and delayed replication of chromosome...... II may reduce the metabolic burden and complexity of chromosome replication by postponing DNA synthesis to the last part of the cell cycle and reducing the need for overlapping replication cycles during rapid proliferation...

  4. Occupational Segregation by Sex: Trends and Prospects.

    Science.gov (United States)

    Blau, Francine D.; Hendricks, Wallace E.

    1979-01-01

    Investigates postwar trends in occupational segregation. Finds segregation increased slightly between 1950-60 as predominantly female clerical/professional jobs increased. Occupation mix changes (1960-70) were neutral in impact, but male inflow into female professions and female inflow into male sales/clerical jobs produced modest segregation…

  5. Ising, Schelling and Self-Organising Segregation

    CERN Document Server

    Stauffer, D

    2007-01-01

    The similarities between phase separation in physics and residential segregation by preference in the Schelling model of 1971 are reviewed. Also, new computer simulations of asymmetric interactions different from the usual Ising model are presented, showing spontaneous magnetisation (= self-organising segregation) and in one case a sharp phase transition.

  6. Ising, Schelling and self-organising segregation

    Science.gov (United States)

    Stauffer, D.; Solomon, S.

    2007-06-01

    The similarities between phase separation in physics and residential segregation by preference in the Schelling model of 1971 are reviewed. Also, new computer simulations of asymmetric interactions different from the usual Ising model are presented, showing spontaneous magnetisation (=self-organising segregation) and in one case a sharp phase transition.

  7. Measuring segregation: an activity space approach.

    Science.gov (United States)

    Wong, David W S; Shaw, Shih-Lung

    2011-06-01

    While the literature clearly acknowledges that individuals may experience different levels of segregation across their various socio-geographical spaces, most measures of segregation are intended to be used in the residential space. Using spatially aggregated data to evaluate segregation in the residential space has been the norm and thus individual's segregation experiences in other socio-geographical spaces are often de-emphasized or ignored. This paper attempts to provide a more comprehensive approach in evaluating segregation beyond the residential space. The entire activity spaces of individuals are taken into account with individuals serving as the building blocks of the analysis. The measurement principle is based upon the exposure dimension of segregation. The proposed measure reflects the exposure of individuals of a referenced group in a neighborhood to the populations of other groups that are found within the activity spaces of individuals in the referenced group. Using the travel diary data collected from the tri-county area in southeast Florida and the imputed racial-ethnic data, this paper demonstrates how the proposed segregation measurement approach goes beyond just measuring population distribution patterns in the residential space and can provide a more comprehensive evaluation of segregation by considering various socio-geographical spaces.

  8. Losing Ground: School Segregation in Massachuestts

    Science.gov (United States)

    Ayscue, Jennifer B.; Greenberg, Alyssa

    2013-01-01

    Though once a leader in school integration, Massachusetts has regressed over the last two decades as its students of color have experienced intensifying school segregation. This report investigates trends in school segregation in Massachusetts by examining concentration, exposure, and evenness measures by both race and class. First, the report…

  9. Undetected sex chromosome aneuploidy by chromosomal microarray.

    Science.gov (United States)

    Markus-Bustani, Keren; Yaron, Yuval; Goldstein, Myriam; Orr-Urtreger, Avi; Ben-Shachar, Shay

    2012-11-01

    We report on a case of a female fetus found to be mosaic for Turner syndrome (45,X) and trisomy X (47,XXX). Chromosomal microarray analysis (CMA) failed to detect the aneuploidy because of a normal average dosage of the X chromosome. This case represents an unusual instance in which CMA may not detect chromosomal aberrations. Such a possibility should be taken into consideration in similar cases where CMA is used in a clinical setting.

  10. Chiasmata promote monopolar attachment of sister chromatids and their co-segregation toward the proper pole during meiosis I.

    Directory of Open Access Journals (Sweden)

    Yukinobu Hirose

    2011-03-01

    Full Text Available The chiasma is a structure that forms between a pair of homologous chromosomes by crossover recombination and physically links the homologous chromosomes during meiosis. Chiasmata are essential for the attachment of the homologous chromosomes to opposite spindle poles (bipolar attachment and their subsequent segregation to the opposite poles during meiosis I. However, the overall function of chiasmata during meiosis is not fully understood. Here, we show that chiasmata also play a crucial role in the attachment of sister chromatids to the same spindle pole and in their co-segregation during meiosis I in fission yeast. Analysis of cells lacking chiasmata and the cohesin protector Sgo1 showed that loss of chiasmata causes frequent bipolar attachment of sister chromatids during anaphase. Furthermore, high time-resolution analysis of centromere dynamics in various types of chiasmate and achiasmate cells, including those lacking the DNA replication checkpoint factor Mrc1 or the meiotic centromere protein Moa1, showed the following three outcomes: (i during the pre-anaphase stage, the bipolar attachment of sister chromatids occurs irrespective of chiasma formation; (ii the chiasma contributes to the elimination of the pre-anaphase bipolar attachment; and (iii when the bipolar attachment remains during anaphase, the chiasmata generate a bias toward the proper pole during poleward chromosome pulling that results in appropriate chromosome segregation. Based on these results, we propose that chiasmata play a pivotal role in the selection of proper attachments and provide a backup mechanism that promotes correct chromosome segregation when improper attachments remain during anaphase I.

  11. Analysis of meiotic segregation, using single-sperm typing: Meiotic drive at the myotonic dystrophy locus

    Energy Technology Data Exchange (ETDEWEB)

    Leeflang, E.P.; Arnheim, N. [Univ. of Southern California, Los Angeles, CA (United States); McPeek, M.S. [Univ. of Chicago, IL (United States)

    1996-10-01

    Meiotic drive at the myotonic dystrophy (DM) locus has recently been suggested as being responsible for maintaining the frequency, in the human population, of DM chromosomes capable of expansion to the disease state. In order to test this hypothesis, we have studied samples of single sperm from three individuals heterozygous at the DM locus, each with one allele larger and one allele smaller than 19 CTG repeats. To guard against the possible problem of differential PCR amplification rates based on the lengths of the alleles, the sperm were also typed at another closely linked marker whose allele size was unrelated to the allele size at the DM locus. Using statistical models specifically designed to study single-sperm segregation data, we find no evidence of meiotic segregation distortion. The upper limit of the two-sided 95% confidence interval for the estimate of the common segregation probability for the three donors is at or below .515 for all models considered, and no statistically significant difference from .5 is detected in any of the models. This suggests that any greater amount of segregation distortion at the myotonic dystrophy locus must result from events following sperm ejaculation. The mathematical models developed make it possible to study segregation distortion with high resolution by using sperm-typing data from any locus. 26 refs., 1 fig., 8 tabs.

  12. Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction

    OpenAIRE

    Reyes, Céline; Serrurier, Céline; Gauthier, Tiphaine; Gachet, Yannick; Tournier, Sylvie

    2015-01-01

    The segregation of centromeres and telomeres at mitosis is coordinated at multiple levels to prevent the formation of aneuploid cells, a phenotype frequently observed in cancer. Mitotic instability arises from chromosome segregation defects, giving rise to chromatin bridges at anaphase. Most of these defects are corrected before anaphase onset by a mechanism involving Aurora B kinase, a key regulator of mitosis in a wide range of organisms. Here, we describe a new role for Aurora B in telomer...

  13. The Spatial Context of Residential Segregation

    CERN Document Server

    Roberto, Elizabeth

    2015-01-01

    Scholars have engaged in a longstanding debate about how best to measure residential segregation, and scores of indexes have been developed in response. However, the methods commonly employed are aspatial -- they summarize the characteristics of segregation patterns, such as concentration or clustering, but ignore their spatial features, such as how neighborhoods are spatially arranged. As a consequence, many studies find the same level of segregation whether a city has a patchwork of racial and ethnic enclaves, or is divided into large areas with little or no diversity. New methods have been developed to capture the spatial proximity of neighborhoods and the geographic scale of clustering. However, they lack a realistic measure of distance and do not accurately represent how segregation varies within cities. In this paper, I introduce a new method for studying the spatial context of residential segregation. I measure the distance between locations along city roads rather than in a straight line. Road distanc...

  14. The bacterial nucleoid: nature, dynamics and sister segregation.

    Science.gov (United States)

    Kleckner, Nancy; Fisher, Jay K; Stouf, Mathieu; White, Martin A; Bates, David; Witz, Guillaume

    2014-12-01

    Recent studies reveal that the bacterial nucleoid has a defined, self-adherent shape and an underlying longitudinal organization and comprises a viscoelastic matrix. Within this shape, mobility is enhanced by ATP-dependent processes and individual loci can undergo ballistic off-equilibrium movements. In Escherichia coli, two global dynamic nucleoid behaviors emerge pointing to nucleoid-wide accumulation and relief of internal stress. Sister segregation begins with local splitting of individual loci, which is delayed at origin, terminus and specialized interstitial snap regions. Globally, as studied in several systems, segregation is a multi-step process in which internal nucleoid state plays critical roles that involve both compaction and expansion. The origin and terminus regions undergo specialized programs partially driven by complex ATP burning mechanisms such as a ParAB Brownian ratchet and a septum-associated FtsK motor. These recent findings reveal strong, direct parallels among events in different systems and between bacterial nucleoids and mammalian chromosomes with respect to physical properties, internal organization and dynamic behaviors.

  15. Mechanisms of plasmid segregation: have multicopy plasmids been overlooked?

    Science.gov (United States)

    Million-Weaver, Samuel; Camps, Manel

    2014-09-01

    Plasmids are self-replicating pieces of DNA typically bearing non-essential genes. Given that plasmids represent a metabolic burden to the host, mechanisms ensuring plasmid transmission to daughter cells are critical for their stable maintenance in the population. Here we review these mechanisms, focusing on two active partition strategies common to low-copy plasmids: par systems type I and type II. Both involve three components: an adaptor protein, a motor protein, and a centromere, which is a sequence area in the plasmid that is recognized by the adaptor protein. The centromere-bound adaptor nucleates polymerization of the motor, leading to filament formation, which can pull plasmids apart (par I) or push them towards opposite poles of the cell (par II). No such active partition mechanisms are known to occur in high copy number plasmids. In this case, vertical transmission is generally considered stochastic, due to the random distribution of plasmids in the cytoplasm. We discuss conceptual and experimental lines of evidence questioning the random distribution model and posit the existence of a mechanism for segregation in high copy number plasmids that moves plasmids to cell poles to facilitate transmission to daughter cells. This mechanism would involve chromosomally-encoded proteins and the plasmid origin of replication. Modulation of this proposed mechanism of segregation could provide new ways to enhance plasmid stability in the context of recombinant gene expression, which is limiting for large-scale protein production and for bioremediation.

  16. Filament depolymerization can pull a chromosome during bacterial mitosis

    Science.gov (United States)

    Banigan, Edward; Gelbart, Michael; Gitai, Zemer; Liu, Andrea; Wingreen, Ned

    2011-03-01

    Chromosome segregation is fundamental to all cells, but the force-generating mechanisms underlying chromosome translocation in bacteria remain mysterious. Caulobacter crescentus utilizes a depolymerization-driven process in which a ParA protein structure elongates from the new cell pole and binds to a ParB-decorated chromosome, and then retracts via disassembly, thus pulling the chromosome across the cell. This poses the question of how a depolymerizing structure can robustly pull the chromosome that is disassembling it. We perform Brownian dynamics simulations with a simple and physically consistent model of the ParABS system. The simulations suggest that the mechanism of translocation is ``self-diffusiophoretic'': by disassembling ParA, ParB generates a ParA concentration gradient so that the concentration of ParA is higher in front of the chromosome than behind it. Since the chromosome is attracted to ParA via ParB, it moves up the ParA gradient and across the cell. We find that translocation is controlled by the product of an effective relaxation time for the chromosome and the rate of ParA disassembly. Our results provide a physical explanation of the mechanism of depolymerization-driven translocation and suggest physical explanations for recent experimental observations.

  17. Mechanics of kinetochore microtubules and their interactions with chromosomes during cell division

    Science.gov (United States)

    Nazockdast, Ehssan; Fürthauer, Sebastian; Redemann, Stephanie; Baumgart, Johannes; Lindow, Norbert; Kratz, Andrea; Prohaska, Steffen; Müller-Reichert, Thomas; Shelley, Michael

    2016-11-01

    The accurate segregation of chromosomes, and subsequent cell division, in Eukaryotic cells is achieved by the interactions of an assembly of microtubules (MTs) and motor-proteins, known as the mitotic spindle. We use a combination of our computational platform for simulating cytoskeletal assemblies and our structural data from high-resolution electron tomography of the mitotic spindle, to study the kinetics and mechanics of MTs in the spindle, and their interactions with chromosomes during chromosome segregation in the first cell division in C.elegans embryo. We focus on kinetochore MTs, or KMTs, which have one end attached to a chromosome. KMTs are thought to be a key mechanical component in chromosome segregation. Using exploratory simulations of MT growth, bending, hydrodynamic interactions, and attachment to chromosomes, we propose a mechanical model for KMT-chromosome interactions that reproduces observed KMT length and shape distributions from electron tomography. We find that including detailed hydrodynamic interactions between KMTs is essential for agreement with the experimental observations.

  18. Orderly Replication and Segregation of the Four Replicons of Burkholderia cenocepacia J2315.

    Directory of Open Access Journals (Sweden)

    Wen-Li Du

    2016-07-01

    Full Text Available Bacterial genomes typically consist of a single chromosome and, optionally, one or more plasmids. But whole-genome sequencing reveals about ten per-cent of them to be multipartite, with additional replicons which by size and indispensability are considered secondary chromosomes. This raises the questions of how their replication and partition is managed without compromising genome stability and of how such genomes arose. Vibrio cholerae, with a 1 Mb replicon in addition to its 3 Mb chromosome, is the only species for which maintenance of a multipartite genome has been investigated. In this study we have explored the more complex genome of Burkholderia cenocepacia (strain J2315. It comprises an extra replicon (c2 of 3.21 Mb, comparable in size to the3.87Mb main chromosome (c1, another extra replicon(c3 of 0.87 Mb and a plasmid of 0.09 Mb. The replication origin of c1 is typically chromosomal and those of c2 and c3 are plasmid-like; all are replicated bidirectionally. Fluorescence microscopy of tagged origins indicates that all initiate replication at mid-cell and segregate towards the cell quarter positions sequentially, c1-c2-p1/c3. c2 segregation is as well-phased with the cell cycle as c1, implying that this plasmid-like origin has become subject to regulation not typical of plasmids; in contrast, c3 segregates more randomly through the cycle. Disruption of individual Par systems by deletion of parAB or by addition of parS sites showed each Par system to govern the positioning of its own replicon only. Inactivation of c1, c2 and c3 Par systems not only reduced growth rate, generated anucleate cells and compromised viability but influenced processes beyond replicon partition, notably regulation of replication, chromosome condensation and cell size determination. In particular, the absence of the c1 ParA protein altered replication of all three chromosomes, suggesting that the partition system of the main chromosome is a major participant in the

  19. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosomes 3. Evidence for the role of chromosome rearrangement in gene amplification

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L.; Munk, A.C.; Longmire, J.L.; Hildebrand, C.E.; Crawford, B.D.

    1984-12-01

    Cadmium resistant (Cd/sup r/) variants with coordinately amplified metallothionein I and II (MTI and MTII) genes have been derived from both Chinese hamster ovary and near-euploid Chinese hamster cell lines. Cytogenetic analyses of Cd/sup r/ variants consistently revealed breakage and rearrangement involving chromosome 3p. In situ hybridization with Chinese hamster MT-encoding cDNA probe localized amplified MT gene sequences near the translocation breakpoint involving chromosome 3p. These observations suggested that both functionally related, isometallothionein loci are linked on Chinese hamster chromosome 3. Southern blot analyses of DNAs isolated from a panel of Chinese hamster x mouse somatic cell hybrids which segregate hamster chromosomes confirmed that both MTI and MTII are located on chromosome 3. The authors speculate that rearrangement of chromosome 3p could be causally involved with the amplification of MT genes in Cd/sup r/ hamster cell lines. 34 references, 3 figures, 1 table.

  20. Modeling density segregation in granular flow

    Science.gov (United States)

    Xiao, Hongyi; Lueptow, Richard; Umbanhowar, Paul

    2015-11-01

    A recently developed continuum-based model accurately predicts segregation in flows of granular mixtures varying in particle size by considering the interplay of advection, diffusion and segregation. In this research, we extend the domain of the model to include density driven segregation. Discrete Element Method (DEM) simulations of density bidisperse flows of mono-sized particles in a quasi-2D bounded heap were performed to determine the dependence of the density driven segregation velocity on local shear rate, particle concentration, and a segregation length which scales with the particle size and the logarithm of the density ratio. With these inputs, the model yields theoretical predictions of density segregation patterns that quantitatively match the DEM simulations over a range of density ratios (1.11-3.33) and flow rates (19.2-113.6 cm3/s). Matching experiments with various combinations of glass, steel and ceramic particles were also performed which reproduced the segregation patterns obtained in both the simulations and the theory.

  1. Chromosome Disorder Outreach

    Science.gov (United States)

    ... BLOG Join Us Donate You are not alone. Chromosome Disorder Outreach, Inc. is a non-profit organization, ... Support For all those diagnosed with any rare chromosome disorder. Since 1992, CDO has supported the parents ...

  2. Pericentric inversion of chromosome 12; a three family study

    DEFF Research Database (Denmark)

    Haagerup, A; Hertz, Jens Michael

    1992-01-01

    rate is calculated to be 0.58, which is not significantly different from an expected segregation rate of 0.5. In family 3, an additional inversion of a chromosome 9 has been found in 4 individuals. Our results are discussed in relation to previous findings and with respect to the genetic counselling......A pericentric inversion of chromosome 12 has been followed in three large independently ascertained Danish families. Out of a total number of 52 persons examined, 25 were found to carry the inversion. The breakpoints in all three families were localized to p13 and q13, resulting in more than one...... of families with pericentric inversions....

  3. REVIEW ARTICLE: DNA protein interactions and bacterial chromosome architecture

    Science.gov (United States)

    Stavans, Joel; Oppenheim, Amos

    2006-12-01

    Bacteria, like eukaryotic organisms, must compact the DNA molecule comprising their genome and form a functional chromosome. Yet, bacteria do it differently. A number of factors contribute to genome compaction and organization in bacteria, including entropic effects, supercoiling and DNA-protein interactions. A gamut of new experimental techniques have allowed new advances in the investigation of these factors, and spurred much interest in the dynamic response of the chromosome to environmental cues, segregation, and architecture, during both exponential and stationary phases. We review these recent developments with emphasis on the multifaceted roles that DNA-protein interactions play.

  4. Veil: A Wall of Segregation

    Directory of Open Access Journals (Sweden)

    Tayebeh Nowrouzi

    2015-08-01

    Full Text Available Moving behind the confines of the race has been the continuous efforts of African-Americans so as to reveal and confirm their true humanity and abilities to white race as well as their own race. African-Americans, Dubois posited, are shut out of the white America, inhabiting behind a vast veil which creates a deep division between the races. Veil is made of the fabric of racism interwoven thread by thread and imposed by white world. It is thrown discourteously and forcibly to the African-Americans whom their distorted images are imposed on them and their true humanity and identity are hidden behind the veil. This study overtakes to present how Loraine Hansberry, in her first and the most outstanding drama, A Raisin in the Sun examines the world within the veil. She demonstrated that Duboisian metaphoric veil is operating in the racist American society so that not only African-Americans are segregated physically and psychologically from the rest of the world but also are inflicted with obscurity of vision that are neither able to see themselves clearly nor be seen truly. On the other hand, it presents how the veil provides blacks with the second sight to observe and comprehend the racist nature of whites which is hidden and incomprehensible for them.

  5. Genes that bias Mendelian segregation.

    Directory of Open Access Journals (Sweden)

    Pierre Grognet

    Full Text Available Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs, complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

  6. Genes that bias Mendelian segregation.

    Science.gov (United States)

    Grognet, Pierre; Lalucque, Hervé; Malagnac, Fabienne; Silar, Philippe

    2014-01-01

    Mendel laws of inheritance can be cheated by Meiotic Drive Elements (MDs), complex nuclear genetic loci found in various eukaryotic genomes and distorting segregation in their favor. Here, we identify and characterize in the model fungus Podospora anserina Spok1 and Spok2, two MDs known as Spore Killers. We show that they are related genes with both spore-killing distorter and spore-protecting responder activities carried out by the same allele. These alleles act as autonomous elements, exert their effects independently of their location in the genome and can act as MDs in other fungi. Additionally, Spok1 acts as a resistance factor to Spok2 killing. Genetical data and cytological analysis of Spok1 and Spok2 localization during the killing process suggest a complex mode of action for Spok proteins. Spok1 and Spok2 belong to a multigene family prevalent in the genomes of many ascomycetes. As they have no obvious cellular role, Spok1 and Spok2 Spore Killer genes represent a novel kind of selfish genetic elements prevalent in fungal genome that proliferate through meiotic distortion.

  7. Centrosome dynamics as a source of chromosomal instability.

    Science.gov (United States)

    Nam, Hyun-Ja; Naylor, Ryan M; van Deursen, Jan M

    2015-02-01

    Accurate segregation of duplicated chromosomes between two daughter cells depends on bipolar spindle formation, a metaphase state in which sister kinetochores are attached to microtubules emanating from opposite spindle poles. To ensure bi-orientation, cells possess surveillance systems that safeguard against microtubule-kinetochore attachment defects, including the spindle assembly checkpoint and the error correction machinery. However, recent developments have identified centrosome dynamics--that is, centrosome disjunction and poleward movement of duplicated centrosomes--as a central target for deregulation of bi-orientation in cancer cells. In this review, we discuss novel insights into the mechanisms that underlie centrosome dynamics and discuss how these mechanisms are perturbed in cancer cells to drive chromosome mis-segregation and advance neoplastic transformation.

  8. A Social Network Analysis of Occupational Segregation

    DEFF Research Database (Denmark)

    Buhai, Ioan Sebastian; van der Leij, Marco

    We develop a social network model of occupational segregation between different social groups, generated by the existence of positive inbreeding bias among individuals from the same group. If network referrals are important for job search, then expected homophily in the contact network structure...... induces different career choices for individuals from different social groups. This further translates into stable occupational segregation equilibria in the labor market. We derive the conditions for wage and unemployment inequality in the segregation equilibria and characterize first and second best...

  9. Genetic Segregation and Genomic Hybridization Patterns Support an Allotetraploid Structure and Disomic Inheritance for Salix Species

    Directory of Open Access Journals (Sweden)

    Gianni Barcaccia

    2014-09-01

    Full Text Available The Salix alba L. (white willow—Salix fragilis L. (crack willow complex includes closely related polyploid species, mainly tetraploid (2n = 4x = 76, which are dioecious and hence obligate allogamous. Because little is known about the genome constitution and chromosome behavior of these pure willow trees, genetic analysis of their naturally occurring interspecific polyploid hybrids is still very difficult. A two-way pseudo-testcross strategy was exploited using single-dose AFLP markers in order to assess the main inheritance patterns of tetraploid biotypes (disomy vs. tetrasomy in segregating populations stemmed from S. alba × S. fragilis crosses and reciprocals. In addition, a genomic in situ hybridization (GISH technology was implemented in willow to shed some light on the genome structure of S. alba and S. fragilis species, and their hybrids (allopolyploidy vs. autopolyploidy. The frequency of S. alba-specific molecular markers was almost double compared to that of S. fragilis-specific ones, suggesting the phylogenetic hypothesis of S. fragilis as derivative species from S. alba-like progenitors. Cytogenetic observations at pro-metaphase revealed about half of the chromosome complements being less contracted than the remaining ones, supporting an allopolyploid origin of both S. alba and S. fragilis. Both genetic segregation and genomic hybridization data are consistent with an allotetraploid nature of the Salix species. In particular, the vast majority of the AFLP markers were inherited according to disomic patterns in S. alba × S. fragilis populations and reciprocals. Moreover, in all S. alba against S. fragilis hybridizations and reciprocals, GISH signals were observed only on the contracted chromosomes whereas the non-contracted chromosomes were never hybridized. In conclusion, half of the chromosomes of the pure species S. alba and S. fragilis are closely related and they could share a common diploid ancestor, while the rest of

  10. Chromosome painting in plants.

    NARCIS (Netherlands)

    Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.

    2001-01-01

    The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in si

  11. ZEBRAFISH CHROMOSOME-BANDING

    NARCIS (Netherlands)

    PIJNACKER, LP; FERWERDA, MA

    1995-01-01

    Banding techniques were carried out on metaphase chromosomes of zebrafish (Danio rerio) embryos. The karyotypes with the longest chromosomes consist of 12 metacentrics, 26 submetacentrics, and 12 subtelocentrics (2n = 50). All centromeres are C-band positive. Eight chromosomes have a pericentric C-b

  12. Chromosome sites play dual roles to establish homologous synapsisduring meiosis in C. elegans

    Energy Technology Data Exchange (ETDEWEB)

    MacQueen, Amy J.; Phillips, Carolyn M.; Bhalla, Needhi; Weiser,Pinky; Villeneuve, Anne M.; Dernburg, Abby F.

    2005-06-05

    required for accurate segregation of homologous chromosomesduring meiosisin C. elegans. We find that these sites play two distinctroles that contribute to proper segregation. Chromosomes lacking PCsusually fail to synapse and also lack a synapsis-independentstabilization activity. The presence of a PC on justone copy of achromosome pair promotes synapsis but does not supportsynapsis-independent pairing stabilization, indicating that thesefunctions are separable. Once initiated, synapsis is highly processive,even between non homologous chromosomes of disparate lengths, elucidatinghow translocations suppress meiotic recombination in C. elegans. Thesefindings suggest a multistep pathway for chromosome synapsis in which PCsimpart selectivity and efficiency through a kinetic proofreadingmechanism. We speculate that concentration of these activities at oneregion per chromosome may have co-evolved with the loss of a pointcentromere to safeguard karyotype stability.

  13. Preferential Breakpoints in the Recovery of Broken Dicentric Chromosomes in Drosophila melanogaster.

    Science.gov (United States)

    Hill, Hunter; Golic, Kent G

    2015-10-01

    We designed a system to determine whether dicentric chromosomes in Drosophila melanogaster break at random or at preferred sites. Sister chromatid exchange in a Ring-X chromosome produced dicentric chromosomes with two bridging arms connecting segregating centromeres as cells divide. This double bridge can break in mitosis. A genetic screen recovered chromosomes that were linearized by breakage in the male germline. Because the screen required viability of males with this X chromosome, the breakpoints in each arm of the double bridge must be closely matched to produce a nearly euploid chromosome. We expected that most linear chromosomes would be broken in heterochromatin because there are no vital genes in heterochromatin, and breakpoint distribution would be relatively unconstrained. Surprisingly, approximately half the breakpoints are found in euchromatin, and the breakpoints are clustered in just a few regions of the chromosome that closely match regions identified as intercalary heterochromatin. The results support the Laird hypothesis that intercalary heterochromatin can explain fragile sites in mitotic chromosomes, including fragile X. Opened rings also were recovered after male larvae were exposed to X-rays. This method was much less efficient and produced chromosomes with a strikingly different array of breakpoints, with almost all located in heterochromatin. A series of circularly permuted linear X chromosomes was generated that may be useful for investigating aspects of chromosome behavior, such as crossover distribution and interference in meiosis, or questions of nuclear organization and function.

  14. Possible segregation caused by centrifugal titanium casting.

    Science.gov (United States)

    Watanabe, K; Okawa, S; Kanatani, M; Nakano, S; Miyakawa, O; Kobayashi, M

    1996-12-01

    The possibility of the segregation under solidification process using a centrifugal casting machine was investigated using an electron probe microanalyzer with elemental distribution map, line analysis and quantitative analysis. When a very small quantity of platinum was added to local molten titanium during the casting process, macroscopic segregation was observed under conditions of density difference of 0.1 g/cm3 at the most, confirming that the centrifugal force of the casting machine is extremely strong. When a Ti-6Al-4V alloy was cast, however, no macroscopic segregation was observed. The centrifugal force of the casting machine examined in the present study hardly results in the body-force segregation in this titanium alloy.

  15. DNA topoisomerase II must act at mitosis to prevent nondisjunction and chromosome breakage.

    OpenAIRE

    Holm, C.; Stearns, T.; Botstein, D

    1989-01-01

    The hypothesis that DNA topoisomerase II facilitates the separation of replicated sister chromatids was tested by examining the consequences of chromosome segregation in the absence of topoisomerase II activity. We observed a substantial elevation in the rate of nondisjunction in top2/top2 cells incubated at the restrictive temperature for one generation time. In contrast, only a minor increase in the amount of chromosome breakage was observed by either physical or genetic assays. These resul...

  16. Chromosome structuring limits genome plasticity in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Emilie Esnault

    2007-12-01

    Full Text Available Chromosome organizations of related bacterial genera are well conserved despite a very long divergence period. We have assessed the forces limiting bacterial genome plasticity in Escherichia coli by measuring the respective effect of altering different parameters, including DNA replication, compositional skew of replichores, coordination of gene expression with DNA replication, replication-associated gene dosage, and chromosome organization into macrodomains. Chromosomes were rearranged by large inversions. Changes in the compositional skew of replichores, in the coordination of gene expression with DNA replication or in the replication-associated gene dosage have only a moderate effect on cell physiology because large rearrangements inverting the orientation of several hundred genes inside a replichore are only slightly detrimental. By contrast, changing the balance between the two replication arms has a more drastic effect, and the recombinational rescue of replication forks is required for cell viability when one of the chromosome arms is less than half than the other one. Macrodomain organization also appears to be a major factor restricting chromosome plasticity, and two types of inverted configurations severely affect the cell cycle. First, the disruption of the Ter macrodomain with replication forks merging far from the normal replichore junction provoked chromosome segregation defects. The second major problematic configurations resulted from inversions between Ori and Right macrodomains, which perturb nucleoid distribution and early steps of cytokinesis. Consequences for the control of the bacterial cell cycle and for the evolution of bacterial chromosome configuration are discussed.

  17. [Homologue pairing: initiation sites and effects on crossing over and chromosome disjunction in Drosophila melanogaster].

    Science.gov (United States)

    Chubykin, V L

    1996-01-01

    The role of homologue pairing and chromocentral association of chromosomes in recombination and segregation during cell division is discussed. Peculiarities of mitotic and meiotic chromosome pairing in Drosophila males and females are considered. On the basis of our own and published data, the presence and localization of sites of homologue pairing initiation in euchromatin are substantiated. The effects of transfer of initiation sites along a chromosome (exemplified by inversions) on chromosome pairing (asynapsis), crossing over (intrachromosomal, interchromosomal, and centromeric effects), and segregation are discussed. To record the effects of pairing sites on crossing over, a method of comparing crossing-over frequencies in an inverted region with those in a region of the same size and position with regard to the centromere on cytological maps was proposed. Chromosomes orient toward opposite division poles during paracentromeric heterochromatin pairing. This occurs after successful euchromatin pairing, during which the chromocentral circular structure is reorganized. If heterochromatin pairing is disrupted because of structural or locus mutations, nonexchange bivalents segregate randomly. In this case, chromosome coordination may occur due to proximal chiasmata or chromocentral associations between homologues.

  18. Gender Segregation in the Spanish Labor Market: An Alternative Approach

    Science.gov (United States)

    del Rio, Coral; Alonso-Villar, Olga

    2010-01-01

    The aim of this paper is to study occupational segregation by gender in Spain, which is a country where occupational segregation explains a large part of the gender wage gap. As opposed to previous studies, this paper measures not only overall segregation, but also the segregation of several population subgroups. For this purpose, this paper uses…

  19. Alteration of chromosome behavior and synchronization of parental chromosomes after successive generations in Brassica napus x Orychophragmus violaceus hybrids.

    Science.gov (United States)

    Zhao, Zhigang; Ma, Ni; Li, Zaiyun

    2007-02-01

    In an earlier study, the progenies of intergeneric hybrids Brassica napus (2n = 38) x Orychophragmus violaceus (2n = 24) were investigated in successive generations (F1-F4) for the cytological phenomenon of parental genome separation during mitotic and meiotic division. In the present study, inbred lines (F5-F8) derived from 1 such hybrid were characterized for morphology, chromosome pairing behaviour, and genome composition. One F5 plant (2n = 31) with slightly yellow petals and 12:19 and 15:16 segregation ratios in its pollen mother cells (PMCs) produced F6 plants with distinct morphological characteristics and wide variations in fertility and chromosome numbers (2n = 25-38). F7 and F8 lines with distinctive morphology and wide ranges in chromsome numbers were established. In PMCs of F7 plants from 4 F6 plants, 0-12 labelled chromosomes from O. violaceus, which predominantly appeared as bivalents, were identified by genomic in situ hybridization. They behaved synchronously with B. napus chromosomes during meiotic division. The results provide molecular cytogenetic evidence of the inclusion of O. violaceus chromosomes in the original hybrids and the cytology in the hybrids documented earlier. They also show that chromosome behaviour was altered and the parental chromosomes became synchronized after successive generations.

  20. Multiple opposing constraints govern chromosome interactions during meiosis.

    Directory of Open Access Journals (Sweden)

    Doris Y Lui

    Full Text Available Homolog pairing and crossing over during meiosis I prophase is required for accurate chromosome segregation to form euploid gametes. The repair of Spo11-induced double-strand breaks (DSB using a homologous chromosome template is a major driver of pairing in many species, including fungi, plants, and mammals. Inappropriate pairing and crossing over at ectopic loci can lead to chromosome rearrangements and aneuploidy. How (or if inappropriate ectopic interactions are disrupted in favor of allelic interactions is not clear. Here we used an in vivo "collision" assay in budding yeast to test the contributions of cohesion and the organization and motion of chromosomes in the nucleus on promoting or antagonizing interactions between allelic and ectopic loci at interstitial chromosome sites. We found that deletion of the cohesin subunit Rec8, but not other chromosome axis proteins (e.g. Red1, Hop1, or Mek1, caused an increase in homolog-nonspecific chromosome interaction, even in the absence of Spo11. This effect was partially suppressed by expression of the mitotic cohesin paralog Scc1/Mdc1, implicating Rec8's role in cohesion rather than axis integrity in preventing nonspecific chromosome interactions. Disruption of telomere-led motion by treating cells with the actin polymerization inhibitor Latrunculin B (Lat B elevated nonspecific collisions in rec8Δ spo11Δ. Next, using a visual homolog-pairing assay, we found that the delay in homolog pairing in mutants defective for telomere-led chromosome motion (ndj1Δ or csm4Δ is enhanced in Lat B-treated cells, implicating actin in more than one process promoting homolog juxtaposition. We suggest that multiple, independent contributions of actin, cohesin, and telomere function are integrated to promote stable homolog-specific interactions and to destabilize weak nonspecific interactions by modulating the elastic spring-like properties of chromosomes.

  1. Chromosomal instability in meningiomas.

    Science.gov (United States)

    van Tilborg, Angela A G; Al Allak, Bushra; Velthuizen, Sandra C J M; de Vries, Annie; Kros, Johan M; Avezaat, Cees J J; de Klein, Annelies; Beverloo, H Berna; Zwarthoff, Ellen C

    2005-04-01

    Approximately 60% of sporadic meningiomas are caused by inactivation of the NF2 tumor suppressor gene on chromosome 22. No causative gene is known for the remaining 40%. Cytogenetic analysis shows that meningiomas caused by inactivation of the NF2 gene can be divided into tumors that show monosomy 22 as the sole abnormality and tumors with a more complex karyotype. Meningiomas not caused by the NF2 gene usually have a diploid karyotype. Here we report that, besides the clonal chromosomal aberrations, the chromosome numbers in many meningiomas varied from one metaphase spread to the other, a feature that is indicative of chromosomal instability. Unexpectedly and regardless of genotype, a subgroup of tumors was observed with an average number of 44.9 chromosomes and little variation in the number of chromosomes per metaphase spread. In addition, a second subgroup was recognized with a hyperdiploid number of chromosomes (average 48.5) and considerable variation in numbers per metaphase. However, this numerical instability resulted in a clonal karyotype with chromosomal gains and losses in addition to loss of chromosome 22 only in meningiomas caused by inactivation of the NF2 gene. In cultured cells of all tumor groups, bi- and multinucleated cells were seen, as well as anaphase bridges, residual chromatid strings, multiple spindle poles, and unseparated chromatids, suggesting defects in the mitotic apparatus or kinetochore. Thus, we conclude that even a benign and slow-growing tumor like a meningioma displays chromosomal instability.

  2. A physical approach to segregation and folding of the Caulobacter crescentus genome.

    Science.gov (United States)

    Dame, Remus T; Tark-Dame, Mariliis; Schiessel, Helmut

    2011-12-01

    Bacterial genomes are functionally organized. This organization is dynamic and globally changing throughout the cell cycle. Upon initiation of replication of the chromosome, the two origins segregate and move towards their new location taking along the newly replicated genome. Caulobacter crescentus employs a dedicated active partitioning (Par) system to move one copy of the parS centromere to the distal pole, while the other stays at the stalked pole. In this issue of Molecular Microbiology, Hong and McAdams describe studies on the speed of segregation of parS and regions up to 150 kb away. They show clear differences in segregation rates between parS and 50 kb flanking regions versus regions further away. To assess segregation rates the authors track fluorescent markers during movement using time-lapse microscopy. The relation between genomic and physical distance of pairs of markers reflects how the genome is folded. This relation permits testing experimental data against models from polymer physics. Such models are helpful in understanding principles of genome folding. Although long used in studies on eukaryotes, this approach has rarely been applied to bacteria. Finally, the authors give the first direct evidence for a role of the bacterial chromatin protein HU in folding the genome in vivo.

  3. Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Fukuda

    2012-02-01

    Full Text Available Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic chromosome axis, including SYCP2, SYCP3, HORMAD1, HORMAD2, SMC3, STAG3, and REC8, become post-translationally modified by phosphorylation during the prophase I stage. We found that HORMAD1 and SMC3 are phosphorylated at a consensus site for the ATM/ATR checkpoint kinase and that the phosphorylated forms of HORMAD1 and SMC3 localize preferentially to unsynapsed chromosomal regions where synapsis has not yet occurred, but not to synapsed or desynapsed regions. We investigated the genetic requirements for the phosphorylation events and revealed that the phosphorylation levels of HORMAD1, HORMAD2, and SMC3 are dramatically reduced in the absence of initiation of meiotic recombination, whereas BRCA1 and SYCP3 are required for normal levels of phosphorylation of HORMAD1 and HORMAD2, but not of SMC3. Interestingly, reduced HORMAD1 and HORMAD2 phosphorylation is associated with impaired targeting of the MSUC (meiotic silencing of unsynapsed chromatin machinery to unsynapsed chromosomes, suggesting that these post-translational events contribute to the regulation of the synapsis surveillance system. We propose that modifications of chromosome axis components serve as signals that facilitate chromosomal events including recombination, checkpoint control, transcription, and synapsis regulation.

  4. Analysis of plant meiotic chromosomes by chromosome painting.

    Science.gov (United States)

    Lysak, Martin A; Mandáková, Terezie

    2013-01-01

    Chromosome painting (CP) refers to visualization of large chromosome regions, entire chromosome arms, or entire chromosomes via fluorescence in situ hybridization (FISH). For CP in plants, contigs of chromosome-specific bacterial artificial chromosomes (BAC) from the target species or from a closely related species (comparative chromosome painting, CCP) are typically applied as painting probes. Extended pachytene chromosomes provide the highest resolution of CP in plants. CP enables identification and tracing of particular chromosome regions and/or entire chromosomes throughout all meiotic stages as well as corresponding chromosome territories in premeiotic interphase nuclei. Meiotic pairing and structural chromosome rearrangements (typically inversions and translocations) can be identified by CP. Here, we describe step-by-step protocols of CP and CCP in plant species including chromosome preparation, BAC DNA labeling, and multicolor FISH.

  5. [Analysis of chromosome composition in interspecific embryonic stem hybrid cells of mice].

    Science.gov (United States)

    Pristiazhniuk, I E; Matveeva, N M; Grafodatskiĭ, A S; Serdiukova, N A; Serov, O L

    2010-01-01

    Chromosome complements of twenty hybrid clones obtained by fusion of Mus musculus embryonic stem cells (ESC) and M. caroli splenocytes were studied. Using of double-color in situ hybridization with chromosome- and species-specific probes we were able to detect the parental origin for each chromosome in hybrid cells. Based on parental chromosome ratio, all 20 hybrid clones were separated in some different groups: from the group containing practically tetraploid M. musculus genome with single M. caroli chromosomes to hybrids with dominance of M. caroli chromosome homologues. In 8 hybrid cells clones we observed prevalence of chromosomes originated from ESC in ratio from 5:1 to 3:1. Another hybrid cells clones have either equal (1:1, 1:2) ratio of M. musculus to M. caroli chromosomes or with the prevalence of ESC- (2:1) or splenocyte- (1:2) originated parental chromosome homologues. In 3 hybrid cells clones, we observed preferable segregation of ESC-originated pluripotent chromosomes. This phenomenon was found for the first time and it possibly indicates compensation of the epigenetic differences between parental chromosomes of ESC- and splenocyte-origination.

  6. Interactive computer program for learning genetic principles of segregation and independent assortment through meiosis.

    Science.gov (United States)

    Yang, Xiaoli; Ge, Rong; Yang, Yufei; Shen, Hao; Li, Yingjie; Tseng, Charles C

    2009-01-01

    Teaching fundamental principles of genetics such as segregation and independent assortment of genes could be challenging for high school and college biology instructors. Students without thorough knowledge in meiosis often end up of frustration and failure in genetics courses. Although all textbooks and laboratory manuals have excellent graphic demonstrations and photographs of meiotic process, students may not always master the concept due to the lack of hands-on exercise. In response to the need for an effective lab exercise to understand the segregation of allelic genes and the independent assortment of the unlinked genes, we developed an interactive program for students to manually manipulate chromosome models and visualize each major step of meiosis so that these two genetic principles can be thoroughly understood.

  7. New insights into human nondisjunction of chromosome 21 in oocytes.

    Directory of Open Access Journals (Sweden)

    Tiffany Renee Oliver

    2008-03-01

    Full Text Available Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1 a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2 a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors.

  8. The Precarious Prokaryotic Chromosome

    OpenAIRE

    Kuzminov, Andrei

    2014-01-01

    Evolutionary selection for optimal genome preservation, replication, and expression should yield similar chromosome organizations in any type of cells. And yet, the chromosome organization is surprisingly different between eukaryotes and prokaryotes. The nuclear versus cytoplasmic accommodation of genetic material accounts for the distinct eukaryotic and prokaryotic modes of genome evolution, but it falls short of explaining the differences in the chromosome organization. I propose that the t...

  9. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteracaea)

    NARCIS (Netherlands)

    Vijverberg, K.; Hulst, van der R.G.M.; Lindhout, W.H.; Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  10. A genetic linkage map of the diplosporous chromosomal region in Taraxacum officinale (common dandelion; Asteraceae)

    NARCIS (Netherlands)

    Vijverberg, Kitty; van der Hulst, R.G.M.; Lindhout, P.; Van Dijk, P.J.

    2004-01-01

    In this study, we mapped the diplosporous chromosomal region in Taraxacum officinale, by using amplified fragment length polymorphism technology (AFLP) in 73 plants from a segregating population. Taraxacum serves as a model system to investigate the genetics, ecology, and evolution of apomixis. The

  11. Chromosomal mosaicism : underlying mechanisms and consequences for early human embryo development

    NARCIS (Netherlands)

    da Avó Ribeiro dos Santos, M.

    2013-01-01

    In humans, reproduction is considered a relatively inefficient process, when compared with other mammalian species and the chance of achieving a spontaneous pregnancy after timed intercourse is at the most 20-30%. Chromosome segregation errors are a well-known inherent feature of cell division in hu

  12. Cohesin SMC1 beta is required for meiotic chromosome dynamics, sister chromatid cohesion and DNA recombination

    NARCIS (Netherlands)

    Revenkova, E.; Eijpe, M.; Heyting, C.; Hodges, C.A.; Hunt, P.A.; Liebe, B.; Scherthan, H.; Jessberger, R.

    2004-01-01

    Sister chromatid cohesion ensures the faithful segregation of chromosomes in mitosis and in both meiotic divisions1, 2, 3, 4. Meiosis-specific components of the cohesin complex, including the recently described SMC1 isoform SMC15, were suggested to be required for meiotic sister chromatid cohesion a

  13. DFNB79: reincarnation of a nonsyndromic deafness locus on chromosome 9q34.3.

    Science.gov (United States)

    Khan, Shahid Yar; Riazuddin, Saima; Shahzad, Mohsin; Ahmed, Nazir; Zafar, Ahmad Usman; Rehman, Atteeq Ur; Morell, Robert J; Griffith, Andrew J; Ahmed, Zubair M; Riazuddin, Sheikh; Friedman, Thomas B

    2010-01-01

    Genetic analysis of an inbred Pakistani family PKDF280, segregating prelingual severe to profound sensorineural hearing loss, provided evidence for a DFNB locus on human chromosome 9q34.3. Co-segregation of the deafness trait with marker D9SH159 was determined by a two-point linkage analysis (LOD score 9.43 at theta=0). Two additional large families, PKDF517 and PKDF741, co-segregate recessive deafness with markers linked to the same interval. Haplotype analyses of these three families refined the interval to 3.84 Mb defined by D9S1818 (centromeric) and D9SH6 (telomeric). This interval overlaps with the previously reported DFNB33 locus whose chromosomal map position has been recently revised and assigned to a new position on chromosome 10p11.23-q21.1. The nonsyndromic deafness locus on chromosome 9q segregating in family PKDF280 was designated DFNB79. We are currently screening the 113 candidate DFNB79 genes for mutations and have excluded CACNA1B, EDF1, PTGDS, EHMT1, QSOX2, NOTCH1, MIR126 and MIR602.

  14. Racial Segregation and the American Foreclosure Crisis.

    Science.gov (United States)

    Rugh, Jacob S; Massey, Douglas S

    2010-10-01

    Although the rise in subprime lending and the ensuing wave of foreclosures was partly a result of market forces that have been well-identified in the literature, in the United States it was also a highly racialized process. We argue that residential segregation created a unique niche of poor minority clients who were differentially marketed risky subprime loans that were in great demand for use in mortgage-backed securities that could be sold on secondary markets. We test this argument by regressing foreclosure actions in the top 100 U.S. metropolitan areas on measures of black, Hispanic, and Asian segregation while controlling for a variety of housing market conditions, including average creditworthiness, the extent of coverage under the Community Reinvestment Act, the degree of zoning regulation, and the overall rate of subprime lending. We find that black residential dissimilarity and spatial isolation are powerful predictors of foreclosures across U.S. metropolitan areas. In order to isolate subprime lending as the causal mechanism whereby segregation influences foreclosures, we estimate a two-stage least squares model that confirms the causal effect of black segregation on the number and rate of foreclosures across metropolitan areas. In the United States segregation was an important contributing cause of the foreclosure crisis, along with overbuilding, risky lending practices, lax regulation, and the bursting of the housing price bubble.

  15. Neurotransmitter segregation: functional and plastic implications.

    Science.gov (United States)

    Sámano, Cynthia; Cifuentes, Fredy; Morales, Miguel Angel

    2012-06-01

    Synaptic cotransmission is the ability of neurons to use more than one transmitter to convey synaptic signals. Cotransmission was originally described as the presence of a classic transmitter, which conveys main signal, along one or more cotransmitters that modulate transmission, later on, it was found cotransmission of classic transmitters. It has been generally accepted that neurons store and release the same set of transmitters in all their synaptic processes. However, some findings that show axon endings of individual neurons storing and releasing different sets of transmitters, are not in accordance with this assumption, and give support to the hypothesis that neurons can segregate transmitters to different synapses. Here, we review the studies showing segregation of transmitters in invertebrate and mammalian central nervous system neurons, and correlate them with our results obtained in sympathetic neurons. Our data show that these neurons segregate even classic transmitters to separated axons. Based on our data we suggest that segregation is a plastic phenomenon and responds to functional synaptic requirements, and to 'environmental' cues such as neurotrophins. We propose that neurons have the machinery to guide the different molecules required in synaptic transmission through axons and sort them to different axon endings. We believe that transmitter segregation improves neuron interactions during cotransmission and gives them selective and better control of synaptic plasticity.

  16. Continuous utility factor in segregation models

    Science.gov (United States)

    Roy, Parna; Sen, Parongama

    2016-02-01

    We consider the constrained Schelling model of social segregation in which the utility factor of agents strictly increases and nonlocal jumps of the agents are allowed. In the present study, the utility factor u is defined in a way such that it can take continuous values and depends on the tolerance threshold as well as the fraction of unlike neighbors. Two models are proposed: in model A the jump probability is determined by the sign of u only, which makes it equivalent to the discrete model. In model B the actual values of u are considered. Model A and model B are shown to differ drastically as far as segregation behavior and phase transitions are concerned. In model A, although segregation can be achieved, the cluster sizes are rather small. Also, a frozen state is obtained in which steady states comprise many unsatisfied agents. In model B, segregated states with much larger cluster sizes are obtained. The correlation function is calculated to show quantitatively that larger clusters occur in model B. Moreover for model B, no frozen states exist even for very low dilution and small tolerance parameter. This is in contrast to the unconstrained discrete model considered earlier where agents can move even when utility remains the same. In addition, we also consider a few other dynamical aspects which have not been studied in segregation models earlier.

  17. Chromosome oscillations in mitosis

    Science.gov (United States)

    Campas, Otger

    2008-03-01

    Successful cell division necessitates a tight regulation of chromosome movement via the activity of molecular motors. Many of the key players at the origin of the forces generating the motion have been identified, but their spatial and temporal organization remains elusive. In animal cells, chromosomes periodically switch between phases of movement towards and away from the pole. This characteristic oscillatory behaviour cannot be explained by the current models of chromosome positioning and congression. We perform a self-contained theoretical analysis in which the motion of mono-oriented chromosomes results from the competition between the activity of the kinetochore and chromokinesin motors on the chromosome arms. Our analysis, consistent with the available experimental data, proposes that the interplay between the aster-like morphology of the spindle and the collective kinetics of molecular motors is at the origin of chromosome oscillations, positioning and congression. It provides a natural explanation for the so-called chromosome directional instability and for the mechanism by which chromosomes sense their position in space. In addition, we estimate the in vivo velocity of chromokinesins at vanishing load and propose new experiments to assess the mechanism at the origin of chromosome movement in cell division.

  18. Mutations to the piRNA pathway component aubergine enhance meiotic drive of segregation distorter in Drosophila melanogaster.

    Science.gov (United States)

    Gell, Selena L; Reenan, Robert A

    2013-03-01

    Diploid sexual reproduction involves segregation of allelic pairs, ensuring equal representation of genotypes in the gamete pool. Some genes, however, are able to "cheat" the system by promoting their own transmission. The Segregation distorter (Sd) locus in Drosophila melanogaster males is one of the best-studied examples of this type of phenomenon. In this system the presence of Sd on one copy of chromosome 2 results in dysfunction of the non-Sd-bearing (Sd(+)) sperm and almost exclusive transmission of Sd to the next generation. The mechanism by which Sd wreaks such selective havoc has remained elusive. However, its effect requires a target locus on chromosome 2 known as Responder (Rsp). The Rsp locus comprises repeated copies of a satellite DNA sequence and Rsp copy number correlates with sensitivity to Sd. Under distorting conditions during spermatogenesis, nuclei with chromosomes containing greater than several hundred Rsp repeats fail to condense chromatin and are eliminated. Recently, Rsp sequences were found as small RNAs in association with Argonaute family proteins Aubergine (Aub) and Argonaute3 (AGO3). These proteins are involved in a germline-specific RNAi mechanism known as the Piwi-interacting RNA (piRNA) pathway, which specifically suppresses transposon activation in the germline. Here, we evaluate the role of piRNAs in segregation distortion by testing the effects of mutations to piRNA pathway components on distortion. Further, we specifically targeted mutations to the aub locus of a Segregation Distorter (SD) chromosome, using ends-out homologous recombination. The data herein demonstrate that mutations to piRNA pathway components act as enhancers of SD.

  19. Resolution of Multimeric Forms of Circular Plasmids and Chromosomes.

    Science.gov (United States)

    Crozat, Estelle; Fournes, Florian; Cornet, François; Hallet, Bernard; Rousseau, Philippe

    2014-10-01

    One of the disadvantages of circular plasmids and chromosomes is their high sensitivity to rearrangements caused by homologous recombination. Odd numbers of crossing-over occurring during or after replication of a circular replicon result in the formation of a dimeric molecule in which the two copies of the replicon are fused. If they are not converted back to monomers, the dimers of replicons may fail to correctly segregate at the time of cell division. Resolution of multimeric forms of circular plasmids and chromosomes is mediated by site-specific recombination, and the enzymes that catalyze this type of reaction fall into two families of proteins: the serine and tyrosine recombinase families. Here we give an overview of the variety of site-specific resolution systems found on circular plasmids and chromosomes.

  20. Segregation of Niobium During Electroslag Remelting Process

    Institute of Scientific and Technical Information of China (English)

    DONG Yan-wu; JIANG Zhou-hua; LI Zheng-bang

    2009-01-01

    Experiment was carried out after the process parameters were calculated by the model previously established.The relationship between interdendritic spacing and local solidification time (LST) mainly determined by process parameters was exposed.Furthermore,the extent of segregation was studied.The results indicate that LST and interdendritic spacing are the largest and the amount of Laves phase as a result of the niobium segregation is the highest in the center of the ingot,whereas the opposite results are obtained at the edge of ingot.The extent of element segregation and the amount of Laves phase can be reduced when appropriate parameters are used.Therefore,the duration of subsequent homogenization treatments for 718 is shortened and the alloy quality is improved.

  1. Segregating complex sound sources through temporal coherence.

    Directory of Open Access Journals (Sweden)

    Lakshmi Krishnan

    2014-12-01

    Full Text Available A new approach for the segregation of monaural sound mixtures is presented based on the principle of temporal coherence and using auditory cortical representations. Temporal coherence is the notion that perceived sources emit coherently modulated features that evoke highly-coincident neural response patterns. By clustering the feature channels with coincident responses and reconstructing their input, one may segregate the underlying source from the simultaneously interfering signals that are uncorrelated with it. The proposed algorithm requires no prior information or training on the sources. It can, however, gracefully incorporate cognitive functions and influences such as memories of a target source or attention to a specific set of its attributes so as to segregate it from its background. Aside from its unusual structure and computational innovations, the proposed model provides testable hypotheses of the physiological mechanisms of this ubiquitous and remarkable perceptual ability, and of its psychophysical manifestations in navigating complex sensory environments.

  2. Fetal chromosome analysis: screening for chromosome disease?

    DEFF Research Database (Denmark)

    Philip, J; Tabor, Ann; Bang, J

    1983-01-01

    The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...... with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications...

  3. The PP2A inhibitor I2PP2A is essential for sister chromatid segregation in oocyte meiosis II.

    Science.gov (United States)

    Chambon, Jean-Philippe; Touati, Sandra A; Berneau, Stéphane; Cladière, Damien; Hebras, Céline; Groeme, Rachel; McDougall, Alex; Wassmann, Katja

    2013-03-18

    Haploid gametes are generated through two consecutive meiotic divisions, with the segregation of chromosome pairs in meiosis I and sister chromatids in meiosis II. Separase-mediated stepwise removal of cohesion, first from chromosome arms and later from the centromere region, is a prerequisite for maintaining sister chromatids together until their separation in meiosis II [1]. In all model organisms, centromeric cohesin is protected from separase-dependent removal in meiosis I through the activity of PP2A-B56 phosphatase, which is recruited to centromeres by shugoshin/MEI-S332 (Sgo) [2-5]. How this protection of centromeric cohesin is removed in meiosis II is not entirely clear; we find that all the PP2A subunits remain colocalized with the cohesin subunit Rec8 at the centromere of metaphase II chromosomes. Here, we show that sister chromatid separation in oocytes depends on a PP2A inhibitor, namely I2PP2A. I2PP2A colocalizes with the PP2A enzyme at centromeres at metaphase II, independently of bipolar attachment. When I2PP2A is depleted, sister chromatids fail to segregate during meiosis II. Our findings demonstrate that in oocytes I2PP2A is essential for faithful sister chromatid segregation by mediating deprotection of centromeric cohesin in meiosis II.

  4. Occurrence of differential meiotic associations and additional chromosomes in the embryo-sac mother cells of Allium roylei Stearn

    Indian Academy of Sciences (India)

    Geeta Sharma; Ravinder N. Gohil

    2011-04-01

    A small population of complex translocation heterozygote plants of Allium roylei from the Bani region of Jammu Province was studied for meiosis in the female track. This study resulted in identification of two variants, having embryo-sac mother cells (EMCs) with more than 16 chromosomes. EMCs of the remaining plants invariably had diploid $(2n = 16)$ chromosome complement. Female meiosis, in general, was found to be abnormal, with nearly 23% and 11% chromosomes associating as quadrivalents or trivalents at prophase I and at metaphase I, respectively. This was followed by irregular segregation of chromosomes at anaphase I. Amongst the variants; one had 38% EMCs with eight bivalents plus two small sized chromosomes. Their small size, dispensable nature and tendency to affect the pairing behaviour of normal complement are some of the features that latter chromosomes share with the B chromosomes. Seventeen to nineteen chromosomes were observed in 35% EMCs of other variant; the remaining cells had 16 chromosomes. Chromosomal behaviour in both kind of cells (euploid and aneuploid) was more or less similar. Unlike female meiocytes, male meiocytes analysed earlier of this strain always had 16 chromosomes which paired to form extremely complex associations involving 3–16 chromosomes. The most likely cause of this asynchrony with regards to number of chromosomes involved in multivalent formation seems to be interaction of genes controlling chiasma formation with the different physiological conditions of male and female meiocytes.

  5. The chromosomal passenger complex activates Polo kinase at centromeres.

    Directory of Open Access Journals (Sweden)

    Mar Carmena

    2012-01-01

    Full Text Available The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC, which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

  6. The chromosomal passenger complex activates Polo kinase at centromeres.

    Science.gov (United States)

    Carmena, Mar; Pinson, Xavier; Platani, Melpi; Salloum, Zeina; Xu, Zhenjie; Clark, Anthony; Macisaac, Fiona; Ogawa, Hiromi; Eggert, Ulrike; Glover, David M; Archambault, Vincent; Earnshaw, William C

    2012-01-01

    The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.

  7. Flow and segregation in sheared granular slurries

    Science.gov (United States)

    Barentin, C.; Azanza, E.; Pouligny, B.

    2004-04-01

    We study the behaviour of a granular slurry, i.e., a very concentrated suspension of heavy (denser than the fluid) and polydisperse particles sheared between two parallel-plane circular disks. For small gaps, the slurry behaves as a 2d system with a characteristic radial size segregation of particles. For large gaps, the slurry responds as a 3d system, with considerable vertical segregation and a concomitant 2-phase (fluid, solid) flow structure. The thickness ζ of the fluid phase is the 2d-3d gap crossover. Surprisingly, ζ is found to be nearly unaffected by very large changes in the particle size distribution.

  8. Housing Systems and Ethnic Spatial Segregation

    DEFF Research Database (Denmark)

    Andersen, Hans Skifter; Andersson, Roger; Wessel, Terje

    in Denmark, Finland, Norway and Sweden are ethnically segmented with high concentrations of immigrants in some forms of tenures (especially social/public housing) and low concentrations in others. The paper shows that the spatial distribution of immigrants is strongly connected with the tenure composition...... of immigrants in social/public housing.......Residential spatial segregation is related to housing markets and housing policies. In this paper, ethnic segregation is compared across four Nordic capitals and explanations for the differences are examined by comparing the housing markets and housing policies of the countries. The housing markets...

  9. Chemical segregation and self polarisation in ferroelectrics

    Directory of Open Access Journals (Sweden)

    Bernard E. Watts

    2009-06-01

    Full Text Available Chemical partitioning or segregation is commonly encountered in solid-state syntheses. It is driven by compositional, thermal and electric field gradients. These phenomena can be quite extreme in thin films and lead to notable effects on the electrical properties of ferroelectrics. The segregation in ferroelectric thin films will be illustrated and the mechanisms explained in terms of diffusion processes driven by a potential gradient of the oxygen. The hypothesis can also explain self polarisation and imprint in ferroelectric hysteresis.

  10. Mitotic Protein CSPP1 Interacts with CENP-H Protein to Coordinate Accurate Chromosome Oscillation in Mitosis.

    Science.gov (United States)

    Zhu, Lijuan; Wang, Zhikai; Wang, Wenwen; Wang, Chunli; Hua, Shasha; Su, Zeqi; Brako, Larry; Garcia-Barrio, Minerva; Ye, Mingliang; Wei, Xuan; Zou, Hanfa; Ding, Xia; Liu, Lifang; Liu, Xing; Yao, Xuebiao

    2015-11-06

    Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. During chromosome alignment, kinetochore-bound microtubules undergo dynamic cycles between growth and shrinkage, leading to an oscillatory movement of chromosomes along the spindle axis. Although kinetochore protein CENP-H serves as a molecular control of kinetochore-microtubule dynamics, the mechanistic link between CENP-H and kinetochore microtubules (kMT) has remained less characterized. Here, we show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. CSPP1 binds to CENP-H in vitro and in vivo. Suppression of CSPP1 perturbs proper mitotic progression and compromises the satisfaction of spindle assembly checkpoint. In addition, chromosome oscillation is greatly attenuated in CSPP1-depleted cells, similar to what was observed in the CENP-H-depleted cells. Importantly, CSPP1 depletion enhances velocity of kinetochore movement, and overexpression of CSPP1 decreases the speed, suggesting that CSPP1 promotes kMT stability during cell division. Specific perturbation of CENP-H/CSPP1 interaction using a membrane-permeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation.

  11. Localization of latency-associated nuclear antigen (LANA) on mitotic chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Rahayu, Retno; Ohsaki, Eriko [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Omori, Hiroko [Central Instrumentation Laboratory Research Institute for Microbial Diseases (BIKEN), Osaka University, Osaka 565-0871 (Japan); Ueda, Keiji, E-mail: kueda@virus.med.osaka-u.ac.jp [Division of Virology, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

    2016-09-15

    In latent infection of Kaposi's sarcoma-associated herpesvirus (KSHV), viral gene expression is extremely limited and copy numbers of viral genomes remain constant. Latency-associated nuclear antigen (LANA) is known to have a role in maintaining viral genome copy numbers in growing cells. Several studies have shown that LANA is localized in particular regions on mitotic chromosomes, such as centromeres/pericentromeres. We independently examined the distinct localization of LANA on mitotic chromosomes during mitosis, using super-resolution laser confocal microscopy and correlative fluorescence microscopy–electron microscopy (FM-EM) analyses. We found that the majority of LANA were not localized at particular regions such as telomeres/peritelomeres, centromeres/pericentromeres, and cohesion sites, but at the bodies of condensed chromosomes. Thus, LANA may undergo various interactions with the host factors on the condensed chromosomes in order to tether the viral genome to mitotic chromosomes and realize faithful viral genome segregation during cell division. - Highlights: • This is the first report showing LANA dots on mitotic chromosomes by fluorescent microscopy followed by electron microscopy. • LANA dots localized randomly on condensed chromosomes other than centromere/pericentromere and telomere/peritelomre. • Cellular mitotic checkpoint should not be always involved in the segregation of KSHV genomes in the latency.

  12. Nucleoporin translocated promoter region (Tpr) associates with dynein complex, preventing chromosome lagging formation during mitosis.

    Science.gov (United States)

    Nakano, Hiroshi; Funasaka, Tatsuyoshi; Hashizume, Chieko; Wong, Richard W

    2010-04-01

    Gain or loss of whole chromosomes is often observed in cancer cells and is thought to be due to aberrant chromosome segregation during mitosis. Proper chromosome segregation depends on a faithful interaction between spindle microtubules and kinetochores. Several components of the nuclear pore complex/nucleoporins play critical roles in orchestrating the rapid remodeling events that occur during mitosis. Our recent studies revealed that the nucleoporin, Rae1, plays critical roles in maintaining spindle bipolarity. Here, we show association of another nucleoporin, termed Tpr (translocated promoter region), with the molecular motors dynein and dynactin, which both orchestrate with the spindle checkpoints Mad1 and Mad2 during cell division. Overexpression of Tpr enhanced multinucleated cell formation. RNA interference-mediated knockdown of Tpr caused a severe lagging chromosome phenotype and disrupted spindle checkpoint proteins expression and localization. Next, we performed a series of rescue and dominant negative experiments to confirm that Tpr orchestrates proper chromosome segregation through interaction with dynein light chain. Our data indicate that Tpr functions as a spatial and temporal regulator of spindle checkpoints, ensuring the efficient recruitment of checkpoint proteins to the molecular motor dynein to promote proper anaphase formation.

  13. XYY chromosome anomaly and schizophrenia.

    Science.gov (United States)

    Rajagopalan, M; MacBeth, R; Varma, S L

    1998-02-07

    Sex chromosome anomalies have been associated with psychoses, and most of the evidence is linked to the presence of an additional X chromosome. We report a patient with XYY chromosome anomaly who developed schizophrenia.

  14. Bulked Segregant Analysis to Detect QTL Related to Heat Tolerance in Rice(Oryza sativa L.)Using SSR Markers

    Institute of Scientific and Technical Information of China (English)

    ZHANG Gui-lian; CHEN Li-yun; XIAO Guo-ying; XIAO Ying-hui; CHEN Xin-bo; ZHANG Shun-tang

    2009-01-01

    The study was undertaken to assess the genetic effect of quantitative trait loci(QTLs)conferring heat tolerance at flowering stage in rice.A population consisting of 279 F2 individuals from the cross between 996,a heat tolerant cultivar and 4628,a heat-sensitive cultivar,was analyzed for their segregation pattern of the difference of seed set rate under optimal temperature condition and high temperature condition.The difference of seed set rate under optimal temperature condition and high temperature condition showed normal distribution,indicating the polygenic control over the trait.To identify main effect of QTL for heat tolerance,the parents were surveyed with 200 primer pairs of simple sequence repeats(SSR).The parental survey revealed 30% polymorphism between parents.In order to detect the main QTL association with heat tolerance,a strategy of combining the DNA pooling from selected segregants and genotyping was adopted.The association of putative markers identified based on DNA pooling from selected segregants was established by single marker analysis(SMA).The results of SMA revealed that SSR markers,RM3735 on chromosome 4 and RM3586 on chromosome 3 showed significant association with heat tolerance respectively.accounted for 17 and 3% of the total variation respectively.The heat tolerance during flowering stage in rice was controlled by multiple gene.The SSR markers,RM3735 on chromosome 4 and RM3586 on chromosome 3 showed significant association with heat tolerance respectively,accounted for 17 and 3% of the total variation respectively.The two genetic loci,especially for RM3735 on chromosome 4,can be used in marker-assistant-selected method in heat tolerance breeding in rice.

  15. Ki-67 acts as a biological surfactant to disperse mitotic chromosomes.

    Science.gov (United States)

    Cuylen, Sara; Blaukopf, Claudia; Politi, Antonio Z; Müller-Reichert, Thomas; Neumann, Beate; Poser, Ina; Ellenberg, Jan; Hyman, Anthony A; Gerlich, Daniel W

    2016-07-14

    Eukaryotic genomes are partitioned into chromosomes that form compact and spatially well-separated mechanical bodies during mitosis. This enables chromosomes to move independently of each other for segregation of precisely one copy of the genome to each of the nascent daughter cells. Despite insights into the spatial organization of mitotic chromosomes and the discovery of proteins at the chromosome surface, the molecular and biophysical bases of mitotic chromosome structural individuality have remained unclear. Here we report that the proliferation marker protein Ki-67 (encoded by the MKI67 gene), a component of the mitotic chromosome periphery, prevents chromosomes from collapsing into a single chromatin mass after nuclear envelope disassembly, thus enabling independent chromosome motility and efficient interactions with the mitotic spindle. The chromosome separation function of human Ki-67 is not confined within a specific protein domain, but correlates with size and net charge of truncation mutants that apparently lack secondary structure. This suggests that Ki-67 forms a steric and electrostatic charge barrier, similar to surface-active agents (surfactants) that disperse particles or phase-separated liquid droplets in solvents. Fluorescence correlation spectroscopy showed a high surface density of Ki-67 and dual-colour labelling of both protein termini revealed an extended molecular conformation, indicating brush-like arrangements that are characteristic of polymeric surfactants. Our study thus elucidates a biomechanical role of the mitotic chromosome periphery in mammalian cells and suggests that natural proteins can function as surfactants in intracellular compartmentalization.

  16. Why Are English Secondary Schools Socially Segregated?

    Science.gov (United States)

    Coldron, John; Cripps, Caroline; Shipton, Lucy

    2010-01-01

    This paper seeks an explanation for the persistent social phenomenon of segregated schooling in England whereby children from families with broadly the same characteristics of wealth, education and social networks are more likely to be educated together and therefore separate from children from more socially distant groups. The paper outlines the…

  17. 17 CFR 31.12 - Segregation.

    Science.gov (United States)

    2010-04-01

    ... convenience be commingled with other leverage customer funds and deposited in the same account or accounts....12 Segregation. (a) Any person that accepts leverage customer funds from a leverage customer to enter into or maintain a leverage contract shall treat and deal with such leverage customer funds...

  18. Calcifying Sorting and Segregating: "Brown" at 60

    Science.gov (United States)

    Graff, Cristina Santamaria; Kozleski, Elizabeth

    2014-01-01

    The 2007 "Parents Involved in Community Schools v. Seattle School District No. 1". Supreme Court 5:4 decision suggests that the Court is divided in its interpretation of "Brown" and its intent in addressing racial segregation. Although "Brown" intended equal educational opportunities through desegregation practices,…

  19. Segregation analysis of urothelial cell carcinoma.

    NARCIS (Netherlands)

    Aben, K.K.H.; Baglietto, L.; Baffoe-Bonnie, A.B.; Coebergh, J.W.W.; Bailey-Wilson, J.E.; Trink, B.; Verbeek, A.L.M.; Schoenberg, M.P.; Witjes, J.A.; Kiemeney, L.A.L.M.

    2006-01-01

    A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of th

  20. Reproductive outcome in 3 families with a satellited chromosome 4 with review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Arn, P.H.; Younie, L.; Russo, S. [Nemours Children`s Clinic, Jacksonville, FL (United States)] [and others

    1995-07-03

    We describe 3 families segregating for a translocation of the nucleolus organizer region (NOR) onto chromosome 4. Review of previously reported cases of translocations involving NOR and chromosome 4 shows that these translocations may be associated with variable reproductive outcomes. We provide evidence that imprinting is not the mechanism responsible for the variable reproductive outcomes in the case of satellited 4p chromosomes; this may offer indirect support for a ribosomal gene position effect. Translocated ribosomal genes may influence the expression of neighboring genes and could explain the variable phenotypes in individuals with satellited nonacrocentric chromosomes. We recommend that prenatal counseling of individuals with satellited nonacrocentric chromosomes should be cautious. 23 refs., 2 figs., 1 tab.

  1. Both Chromosome Decondensation and Condensation Are Dependent on DNA Replication in C. elegans Embryos.

    Science.gov (United States)

    Sonneville, Remi; Craig, Gillian; Labib, Karim; Gartner, Anton; Blow, J Julian

    2015-07-21

    During cell division, chromatin alternates between a condensed state to facilitate chromosome segregation and a decondensed form when DNA replicates. In most tissues, S phase and mitosis are separated by defined G1 and G2 gap phases, but early embryogenesis involves rapid oscillations between replication and mitosis. Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA. In addition, we found that, during late telophase, replication initiates on condensed chromosomes and promotes the rapid decondensation of the chromatin. Upon replication initiation, the CDC-45-MCM-GINS (CMG) DNA helicase drives the release of condensin I complexes from chromatin and the activation or displacement of inactive MCM-2-7 complexes, which together with the nucleoporin MEL-28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation. Our results show how, in an early embryo, the chromosome-condensation cycle is functionally linked with DNA replication.

  2. Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria decumbens (Poaceae)

    Indian Academy of Sciences (India)

    Gléia Cristina Laverde Ricci; Alice Maria De Souza-Kaneshima; Mariana Ferrari Felismino; Andrea Beatriz Mendes-Bonato; Maria Suely Pagliarini; Cacilda Borges Do Valle

    2011-08-01

    A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them, 15 accessions presented $2n = 18$; 27 accessions, $2n = 36$; and 2 accessions, $2n = 45$ chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions.

  3. Chromosome numbers and meiotic analysis in the pre-breeding of Brachiaria decumbens (Poaceae).

    Science.gov (United States)

    Ricci, Gléia Cristina Laverde; De Souza-Kaneshima, Alice Maria; Felismino, Mariana Ferrari; Mendes-Bonato, Andrea Beatriz; Pagliarini, Maria Suely; Do Valle, Cacilda Borges

    2011-08-01

    A total of 44 accessions of Brachiaria decumbens were analysed for chromosome count and meiotic behaviour in order to identify potential progenitors for crosses. Among them, 15 accessions presented 2n = 18; 27 accessions, 2n = 36; and 2 accessions, 2n = 45 chromosomes. Among the diploid accessions, the rate of meiotic abnormalities was low, ranging from 0.82% to 7.93%. In the 27 tetraploid accessions, the rate of meiotic abnormalities ranged from 18.41% to 65.83%. The most common meiotic abnormalities were related to irregular chromosome segregation, but chromosome stickiness and abnormal cytokinesis were observed in low frequency. All abnormalities can compromise pollen viability by generating unbalanced gametes. Based on the chromosome number and meiotic stability, the present study indicates the apomictic tetraploid accessions that can act as male genitor to produce interspecific hybrids with B. ruziziensis or intraspecific hybrids with recently artificially tetraploidized accessions.

  4. Involvement of regions of the 4th and 7th chromosomes in the open-field activity of mice.

    Science.gov (United States)

    Clément, Y; Martin, B; Venault, P; Chapouthier, G

    1995-09-01

    Reactivity to a new environment was studied in mice, using an open-field procedure in two strains, C57BL/6By and ABP/Le, the F1 populations and the intercrosses F2 and backcross segregating populations. The analysis of the behavioral traits: peripheral and central activities, leaning, rearing and defecation in the parental strains made it possible to show that the ABP/Le strain was more reactive than C57BL/6By. In addition, the study of segregating, for four phenotypic markers, in F2 and backcross populations strongly suggested that two autosomal regions were involved in the control of open-field behavior: one in chromosomal region comprising the b locus on chromosome 4 and one in chromosomal region comprising the p locus on chromosome 7.

  5. Modeling size segregation of granular materials: the roles of segregation, advection and diffusion

    CERN Document Server

    Fan, Yi; Umbanhowar, Paul B; Ottino, Julio M; Lueptow, Richard M

    2014-01-01

    Predicting segregation of granular materials composed of different-sized particles is a challenging problem. In this paper, we develop and implement a theoretical model that captures the interplay between advection, segregation, and diffusion in size bidisperse granular materials. The fluxes associated with these three driving factors depend on the underlying kinematics, whose characteristics play key roles in determining particle segregation configurations. Unlike previous models for segregation, our model uses parameters based on kinematic measures from discrete element method simulations instead of arbitrarily adjustable fitting parameters, and it achieves excellent quantitative agreement with both experimental and simulation results when applied to quasi-two-dimensional bounded heaps. The model yields two dimensionless control parameters, both of which are only functions of physically control parameters (feed rate, particle sizes, and system size) and kinematic parameters (diffusion coefficient, flowing l...

  6. Sequential cloning of chromosomes

    Science.gov (United States)

    Lacks, S.A.

    1995-07-18

    A method for sequential cloning of chromosomal DNA of a target organism is disclosed. A first DNA segment homologous to the chromosomal DNA to be sequentially cloned is isolated. The first segment has a first restriction enzyme site on either side. A first vector product is formed by ligating the homologous segment into a suitably designed vector. The first vector product is circularly integrated into the target organism`s chromosomal DNA. The resulting integrated chromosomal DNA segment includes the homologous DNA segment at either end of the integrated vector segment. The integrated chromosomal DNA is cleaved with a second restriction enzyme and ligated to form a vector-containing plasmid, which is replicated in a host organism. The replicated plasmid is then cleaved with the first restriction enzyme. Next, a DNA segment containing the vector and a segment of DNA homologous to a distal portion of the previously isolated DNA segment is isolated. This segment is then ligated to form a plasmid which is replicated within a suitable host. This plasmid is then circularly integrated into the target chromosomal DNA. The chromosomal DNA containing the circularly integrated vector is treated with a third, retrorestriction (class IIS) enzyme. The cleaved DNA is ligated to give a plasmid that is used to transform a host permissive for replication of its vector. The sequential cloning process continues by repeated cycles of circular integration and excision. The excision is carried out alternately with the second and third enzymes. 9 figs.

  7. Chromosomal mosaicism goes global

    Directory of Open Access Journals (Sweden)

    Yurov Yuri B

    2008-11-01

    Full Text Available Intercellular differences of chromosomal content in the same individual are defined as chromosomal mosaicism (alias intercellular or somatic genomic variations or, in a number of publications, mosaic aneuploidy. It has long been suggested that this phenomenon poorly contributes both to intercellular (interindividual diversity and to human disease. However, our views have recently become to change due to a series of communications demonstrated a higher incidence of chromosomal mosaicism in diseased individuals (major psychiatric disorders and autoimmune diseases as well as depicted chromosomal mosaicism contribution to genetic diversity, the central nervous system development, and aging. The later has been produced by significant achievements in the field of molecular cytogenetics. Recently, Molecular Cytogenetics has published an article by Maj Hulten and colleagues that has provided evidences for chromosomal mosaicism to underlie formation of germline aneuploidy in human female gametes using trisomy 21 (Down syndrome as a model. Since meiotic aneuploidy is suggested to be the leading genetic cause of human prenatal mortality and postnatal morbidity, these data together with previous findings define chromosomal mosaicism not as a casual finding during cytogenetic analyses but as a more significant biological phenomenon than previously recognized. Finally, the significance of chromosomal mosaicism can be drawn from the fact, that this phenomenon is involved in genetic diversity, normal and abnormal prenatal development, human diseases, aging, and meiotic aneuploidy, the intrinsic cause of which remains, as yet, unknown.

  8. Control on Housing Segregation:Housing Modes and Public Policies

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>1. Housing segregation:advocating or controlling?The phenomenon of housing segregation has become more and more obvious in Chinese cities in recent years; however, there is no agreement on whether it should

  9. CHROMOSOMES OF AMERICAN MARSUPIALS.

    Science.gov (United States)

    BIGGERS, J D; FRITZ, H I; HARE, W C; MCFEELY, R A

    1965-06-18

    Studies of the chromosomes of four American marsupials demonstrated that Caluromys derbianus and Marmosa mexicana have a diploid number of 14 chromosomes, and that Philander opossum and Didelphis marsupialis have a diploid number of 22. The karyotypes of C. derbianus and M. mexicana are similar, whereas those of P. opossum and D. marsupialis are dissimilar. If the 14-chromosome karyotype represents a reduction from a primitive number of 22, these observations suggest that the change has occurred independently in the American and Australasian forms.

  10. Within-School Segregation in an Urban School District

    Science.gov (United States)

    Conger, Dylan

    2005-01-01

    This article examines ethnic segregation, defined as segregation among racial groups as well as between native-born and immigrant students, across elementary school classrooms in New York City. Specifically, the study compares patterns in within-school segregation across ethnic groups, grades, boroughs, and years. Current levels of within-school…

  11. Testing sexual segregation and aggregation: old ways are best.

    Science.gov (United States)

    Bonenfant, Christophe; Gaillard, Jean-michel; Dray, Stéphane; Loison, Anne; Royer, Manuela; Chessel, Daniel

    2007-12-01

    The study of sexual segregation has received increasing attention over the last two decades. Several hypotheses have been proposed to explain the existence of sexual segregation, such as the "predation risk hypothesis," the "forage selection hypothesis," and the "activity budget hypothesis." Testing which hypothesis drives sexual segregation is hampered, however, by the lack of consensus regarding a formal measurement of sexual segregation. By using a derivation of the well-known chi-square (here called the sexual segregation and aggregation statistic [SSAS]) instead of existent segregation coefficients, we offer a reliable way to test for temporal variation in the occurrence of sexual segregation and aggregation, even in cases where a large proportion of animals are observed alone. A randomization procedure provides a test for the null hypothesis of independence of the distributions of males and females among the groups. The usefulness of SSAS in the study of sexual segregation is demonstrated with three case studies on ungulate populations belonging to species with contrasting life histories and annual grouping patterns (isard, red deer, and roe deer). The existent segregation coefficients were unreliable since, for a given value, sexual segregation could or could not occur. Similarly, the existent segregation coefficients performed badly when males and females aggregated. The new SSAS was not prone to such limitations and allowed clear conclusions regarding whether males and females segregate, aggregate, or simply mix at random applicable to all species.

  12. Residential segregation of socioeconomic variables and health indices in Iran

    Directory of Open Access Journals (Sweden)

    Seyed Saeed Hashemi Nazari

    2013-01-01

    Conclusions: Correlation of segregation of determinants of socioeconomic status with segregation of health indices is an indicator of existence of hot zones of health problems across some provinces. Further studies using multilevel modeling and individual data in health outcomes at individual level and segregation measures at appropriate geographic levels are required to confirm these relations.

  13. "E Pluribus"... Separation: Deepening Double Segregation for More Students

    Science.gov (United States)

    Orfield, Gary; Kucsera, John; Siegel-Hawley, Genevieve

    2012-01-01

    This report shows segregation has increased dramatically across the country for Latino students, who are attending more intensely segregated and impoverished schools than they have for generations. The segregation increases have been the most dramatic in the West. The typical Latino student in the region attends a school where less than a quarter…

  14. 46 CFR 151.13-5 - Cargo segregation-tanks.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Cargo segregation-tanks. 151.13-5 Section 151.13-5... CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Cargo Segregation § 151.13-5 Cargo segregation—tanks. (a... symbols used in lines 1 and 2, in order, under the tank segregation column of Table 151.05....

  15. Chromosomal abnormalities and autism

    Directory of Open Access Journals (Sweden)

    Farida El-Baz

    2016-01-01

    Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.

  16. Quantitative Trait Loci Mapping for Bacterial Blight Resistance in Rice Using Bulked Segregant Analysis

    Directory of Open Access Journals (Sweden)

    Xueying Han

    2014-07-01

    Full Text Available Oryza meyeriana is highly resistant to rice bacterial blight (BB and this resistance trait has been transferred to cultivated rice (O. sativa using asymmetric somatic hybridization. However, no resistance genes have yet been cloned. In the present study, a progeny of the somatic hybridization with high BB resistance was crossed with a rice cultivar with high BB susceptibility to develop an F2 population. Using bulked segregant analysis (BSA, 17 polymorphic markers that were linked to rice BB resistance were obtained through scanning a total of 186 simple sequence repeats (SSR and sequence-tagged site (STS markers, evenly distributed on 12 chromosomes. A genetic linkage map was then constructed based on the 17 linkage markers and the F2 segregating population, which was followed by mapping for quantitative trait loci (QTLs for BB resistance. Three QTLs were identified on chromosomes 1, 3 and 5, respectively, and the alleles of the resistant parent at any of the QTLs increased BB resistance. All of the three QTLs had a strong effect on resistance, explaining about 21.5%, 12.3% and 39.2% of the resistance variance, respectively. These QTLs were different from the loci of the BB resistance genes that have been identified in previous studies. The QTLs mapped in this work will facilitate the isolation of novel BB resistance genes and their utilization in rice resistance breeding.

  17. [Sex chromosomes and meiosis].

    Science.gov (United States)

    Guichaoua, M-R; Geoffroy-Siraudin, C; Tassistro, V; Ghalamoun-Slaimi, R; Perrin, J; Metzler-Guillemain, C

    2009-01-01

    Sex chromosome behaviour fundamentally differs between male and female meiosis. In oocyte, X chromosomes synapse giving a XX bivalent which is not recognizable in their morphology and behaviour from autosomal bivalents. In human male, X and Y chromosomes differ from one another in their morphology and their genetic content, leading to a limited pairing and preventing genetic recombination, excepted in homologous region PAR1. During pachytene stage of the first meiotic prophase, X and Y chromosomes undergo a progressive condensation and form a transcriptionally silenced peripheral XY body. The condensation of the XY bivalent during pachytene stage led us to describe four pachytene substages and to localize the pachytene checkpoint between substages 2 and 3. We also defined the pachytene index (PI=P1+P2/P1+P2+P3+P4) which is always less than 0.50 in normal meiosis. XY body undergoes decondensation at diplotene stage, but transcriptional inactivation of the two sex chromosomes or Meiotic Sex Chromosome Inactivation (MSCI) persists through to the end of spermatogenesis. Sex chromosome inactivation involves several proteins, some of them were now identified. Two isoforms of the HP1 protein, HP1beta and HP1gamma, are involved in the facultative heterochromatinization of the XY body, but the initiation of this process involves the phosphorylation of the protein H2AX by the kinase ATR whose recruitment depends on BRCA1. Extensive researches on the inactivation of the sex chromosomes during male meiosis will allow to a better understanding of some male infertilities.

  18. Chromosome doubling method

    Science.gov (United States)

    Kato, Akio

    2006-11-14

    The invention provides methods for chromosome doubling in plants. The technique overcomes the low yields of doubled progeny associated with the use of prior techniques for doubling chromosomes in plants such as grasses. The technique can be used in large scale applications and has been demonstrated to be highly effective in maize. Following treatment in accordance with the invention, plants remain amenable to self fertilization, thereby allowing the efficient isolation of doubled progeny plants.

  19. Activation of X Chromosome Inactivation

    NARCIS (Netherlands)

    C.M. Maduro (Cheryl)

    2016-01-01

    markdownabstractIn mammals, males are the heterogametic sex having an X chromosome and a Y chromosome whereas females have two X chromosomes. Despite originating from an ancient homologous autosomal pair, the X and Y chromosome now differ greatly in size and gene content after ~180 MY of evolution.

  20. Effect of weightlessness on colloidal particle transport and segregation in self-organising microtubule preparations.

    Science.gov (United States)

    Tabony, James; Rigotti, Nathalie; Glade, Nicolas; Cortès, Sandra

    2007-05-01

    Weightlessness is known to effect cellular functions by as yet undetermined processes. Many experiments indicate a role of the cytoskeleton and microtubules. Under appropriate conditions in vitro microtubule preparations behave as a complex system that self-organises by a combination of reaction and diffusion. This process also results in the collective transport and organisation of any colloidal particles present. In large centimetre-sized samples, self-organisation does not occur when samples are exposed to a brief early period of weightlessness. Here, we report both space-flight and ground-based (clinorotation) experiments on the effect of weightlessness on the transport and segregation of colloidal particles and chromosomes. In centimetre-sized containers, both methods show that a brief initial period of weightlessness strongly inhibits particle transport. In miniature cell-sized containers under normal gravity conditions, the particle transport that self-organisation causes results in their accumulation into segregated regions of high and low particle density. The gravity dependence of this behaviour is strongly shape dependent. In square wells, neither self-organisation nor particle transport and segregation occur under conditions of weightlessness. On the contrary, in rectangular canals, both phenomena are largely unaffected by weightlessness. These observations suggest, depending on factors such as cell and embryo shape, that major biological functions associated with microtubule driven particle transport and organisation might be strongly perturbed by weightlessness.

  1. Mechanism of DNA Segregation in Prokaryotes: Replicon Pairing by parC of Plasmid R1

    Science.gov (United States)

    Jensen, Rasmus Bugge; Lurz, Rudi; Gerdes, Kenn

    1998-07-01

    Prokaryotic chromosomes and plasmids encode partitioning systems that are required for DNA segregation at cell division. The systems are thought to be functionally analogous to eukaryotic centromeres and to play a general role in DNA segregation. The parA system of plasmid R1 encodes two proteins ParM and ParR, and a cis-acting centromere-like site denoted parC. The ParR protein binds to parC in vivo and in vitro. The ParM protein is an ATPase that interacts with ParR specifically bound to parC. Using electron microscopy, we show here that parC mediates efficient pairing of plasmid molecules. The pairing requires binding of ParR to parC and is stimulated by the ParM ATPase. The ParM mediated stimulation of plasmid pairing is dependent on ATP hydrolysis by ParM. Using a ligation kinetics assay, we find that ParR stimulates ligation of parC-containing DNA fragments. The rate-of-ligation was increased by wild type ParM protein but not by mutant ParM protein deficient in the ATPase activity. Thus, two independent assays show that parC mediates pairing of plasmid molecules in vitro. These results are consistent with the proposal that replicon pairing is part of the mechanism of DNA segregation in prokaryotes.

  2. Screening of medicinal plants for induction of somatic segregation activity in Aspergillus nidulans.

    Science.gov (United States)

    Ramos Ruiz, A; De la Torre, R A; Alonso, N; Villaescusa, A; Betancourt, J; Vizoso, A

    1996-07-05

    Knowledge about mutagenic properties of plants commonly used in traditional medicine is limited. A screening for genotoxic activity was carried out in aqueous or alcoholic extracts prepared from 13 medicinal plants widely used as folk medicine in Cuba: Lepidium virginicum L. (Brassicaceae): Plantago major L. and Plantago lanceolata L. (Plantaginaceae); Ortosiphon aristatus Blume, Mentha x piperita L., Melissa officinalis L. and Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Cymbopogon citratus (DC.) Stapf (Poaceae); Passiflora incarnata L. (Passifloraceae); Zingiber officinale Roscoe (Zingiberaceae); Piper auritum HBK. (Piperaceae); Schinus terebinthifolius Raddi (Anacardeaceae) and Momordica charantia L. (Cucurbitaceae). A plate incorporation assay with Aspergillus nidulans was employed, allowing detection of somatic segregation as a result of mitotic crossing-over, chromosome malsegregation or clastogenic effects. Aspergillus nidulans D-30, a well-marked strain carrying four recessive mutations for conidial color in heterozygosity, which permitted the direct visual detection of segregants, was used throughout this study. As a result, only in the aqueous extract of one of the plants screened (Momordica charantia) a statistical significant increase in the frequency of segregant sectors per colony was observed, and consequently, a genotoxic effect is postulated.

  3. Physical Modeling of Dynamic Coupling between Chromosomal Loci.

    Science.gov (United States)

    Lampo, Thomas J; Kennard, Andrew S; Spakowitz, Andrew J

    2016-01-19

    The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.

  4. pain2: A neuropathic pain QTL identified on rat chromosome 2.

    Science.gov (United States)

    Nissenbaum, Jonathan; Shpigler, Hagai; Pisanté, Anne; DelCanho, Sonia; Minert, Anne; Seltzer, Ze'ev; Devor, Marshall; Darvasi, Ariel

    2008-03-01

    We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus) based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus musculus). The work was based on rat selection lines HA (high autotomy) and LA (low autotomy) which show a contrasting pain phenotype in response to nerve injury in the neuroma model of neuropathic pain. An F(2) segregating population was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on chromosome 7 and chromosome 2, regions that share a partial homology with mouse chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63 (corresponding to p=0.005 after correcting for multiple testing using permutations) on rat chromosome 2, which is suggestive of the presence of a QTL affecting the predisposition to neuropathic pain. This QTL was mapped to the 14-26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse chromosome 13, rather than to the region of mouse chromosome 15 that contains pain1. This chromosomal position indicates that it is possibly a new QTL, and hence we name it pain2. Further work is needed to replicate and to uncover the underlying gene(s) in both species.

  5. From Schelling to Schools : A comparison of a model of residential segregation with a model of school segregation

    NARCIS (Netherlands)

    Stoica, Victor; Flache, Andreas

    2014-01-01

    We address theoretically whether and under what conditions Schelling's celebrated result of 'self-organized' unintended residential segregation may also apply to school segregation. We propose here a computational model of school segregation that is aligned with a corresponding Schelling-type model

  6. Vibrio chromosomes share common history

    Directory of Open Access Journals (Sweden)

    Gevers Dirk

    2010-05-01

    Full Text Available Abstract Background While most gamma proteobacteria have a single circular chromosome, Vibrionales have two circular chromosomes. Horizontal gene transfer is common among Vibrios, and in light of this genetic mobility, it is an open question to what extent the two chromosomes themselves share a common history since their formation. Results Single copy genes from each chromosome (142 genes from chromosome I and 42 genes from chromosome II were identified from 19 sequenced Vibrionales genomes and their phylogenetic comparison suggests consistent phylogenies for each chromosome. Additionally, study of the gene organization and phylogeny of the respective origins of replication confirmed the shared history. Conclusions Thus, while elements within the chromosomes may have experienced significant genetic mobility, the backbones share a common history. This allows conclusions based on multilocus sequence analysis (MLSA for one chromosome to be applied equally to both chromosomes.

  7. Socio-Spatial Segregations in Social Media

    Directory of Open Access Journals (Sweden)

    Murat SEIFY

    2016-12-01

    Full Text Available In conjunction with developments in communication technologies, life spaces of people also change and develop. What constitutes the most important building block of these new life spaces are digital communication resources. Digital communication resources form new spaces in social media by manipulating identities and cultures. These new spaces create socio-spatial segregations, whether consciously or unconsciously. Especially in recent years, grouping is observed intensely in social media and from time to time these groups play an important role in mass actions. In this study, closed and secret groups formed in social media were examined, with qualitative and quantitative research methods. Within this context, through in-depth interviews with group admins and survey study with group members, socio-spatial segregation in social media and grouping processes in social media were examined.

  8. Phase diagram of a Schelling segregation model

    Science.gov (United States)

    Gauvin, L.; Vannimenus, J.; Nadal, J.-P.

    2009-07-01

    The collective behavior in a variant of Schelling’s segregation model is characterized with methods borrowed from statistical physics, in a context where their relevance was not conspicuous. A measure of segregation based on cluster geometry is defined and several quantities analogous to those used to describe physical lattice models at equilibrium are introduced. This physical approach allows to distinguish quantitatively several regimes and to characterize the transitions between them, leading to the building of a phase diagram. Some of the transitions evoke empirical sudden ethnic turnovers. We also establish links with ‘spin-1’ models in physics. Our approach provides generic tools to analyze the dynamics of other socio-economic systems.

  9. Phase Segregation in Polystyrene?Polylactide Blends

    Energy Technology Data Exchange (ETDEWEB)

    Leung, Bonnie; Hitchcock, Adam; Brash, John; Scholl, Andreas; Doran, Andrew

    2010-06-09

    Spun-cast films of polystyrene (PS) blended with polylactide (PLA) were visualized and characterized using atomic force microscopy (AFM) and synchrotron-based X-ray photoemission electron microscopy (X-PEEM). The composition of the two polymers in these systems was determined by quantitative chemical analysis of near-edge X-ray absorption signals recorded with X-PEEM. The surface morphology depends on the ratio of the two components, the total polymer concentration, and the temperature of vacuum annealing. For most of the blends examined, PS is the continuous phase with PLA existing in discrete domains or segregated to the air?polymer interface. Phase segregation was improved with further annealing. A phase inversion occurred when films of a 40:60 PS:PLA blend (0.7 wt percent loading) were annealed above the glass transition temperature (Tg) of PLA.

  10. DYNLT3 is required for chromosome alignment during mouse oocyte meiotic maturation.

    Science.gov (United States)

    Huang, Xin; Wang, Hai-Long; Qi, Shu-Tao; Wang, Zhen-Bo; Tong, Jing-Shan; Zhang, Qing-Hua; Ouyang, Ying-Chun; Hou, Yi; Schatten, Heide; Qi, Zhong-Quan; Sun, Qing-Yuan

    2011-10-01

    Dynein light chain, Tctex-type 3 (DYNLT3), is a member of the cytoplasmic dynein DYNLT light chain family and has been reported to have a potential role in chromosome congression in human mitosis. However, its role in mammalian meiosis is unclear. In this study, we examined its localization, expression, and functions in mouse oocyte meiosis. Immunofluorescent staining showed that DYNLT3 was restricted to the germinal vesicle and associated with kinetochores at the germinal vesicle breakdown stage, metaphase I and metaphase II. The expression level of DYNLT3 was similar at all meiotic stages. Depletion of DYNLT3 by antibody injection resulted in chromosome misalignment and decrease of the polar body extrusion rate. We further found that DYNLT3-depleted oocytes displayed kinetochore-microtubule detachments. Chromosome-spread experiments showed that depletion of DYNLT3 inhibited the metaphase-anaphase transition by preventing homologous chromosome segregation in meiosis I. Our data suggest that DYNLT3 is required for chromosome alignment and homologous chromosome segregation during mouse oocyte meiosis.

  11. Centromere-independent accumulation of cohesin at ectopic heterochromatin sites induces chromosome stretching during anaphase.

    Directory of Open Access Journals (Sweden)

    Raquel A Oliveira

    2014-10-01

    Full Text Available Pericentric heterochromatin, while often considered as "junk" DNA, plays important functions in chromosome biology. It contributes to sister chromatid cohesion, a process mediated by the cohesin complex that ensures proper genome segregation during nuclear division. Long stretches of heterochromatin are almost exclusively placed at centromere-proximal regions but it remains unclear if there is functional (or mechanistic importance in linking the sites of sister chromatid cohesion to the chromosomal regions that mediate spindle attachment (the centromere. Using engineered chromosomes in Drosophila melanogaster, we demonstrate that cohesin enrichment is dictated by the presence of heterochromatin rather than centromere proximity. This preferential accumulation is caused by an enrichment of the cohesin-loading factor (Nipped-B/NIPBL/Scc2 at dense heterochromatic regions. As a result, chromosome translocations containing ectopic pericentric heterochromatin embedded in euchromatin display additional cohesin-dependent constrictions. These ectopic cohesion sites, placed away from the centromere, disjoin abnormally during anaphase and chromosomes exhibit a significant increase in length during anaphase (termed chromatin stretching. These results provide evidence that long stretches of heterochromatin distant from the centromere, as often found in many cancers, are sufficient to induce abnormal accumulation of cohesin at these sites and thereby compromise the fidelity of chromosome segregation.

  12. Heterochromatic threads connect oscillating chromosomes during prometaphase I in Drosophila oocytes.

    Directory of Open Access Journals (Sweden)

    Stacie E Hughes

    2009-01-01

    Full Text Available In Drosophila oocytes achiasmate homologs are faithfully segregated to opposite poles at meiosis I via a process referred to as achiasmate homologous segregation. We observed that achiasmate homologs display dynamic movements on the meiotic spindle during mid-prometaphase. An analysis of living prometaphase oocytes revealed both the rejoining of achiasmate X chromosomes initially located on opposite half-spindles and the separation toward opposite poles of two X chromosomes that were initially located on the same half spindle. When the two achiasmate X chromosomes were positioned on opposite halves of the spindle their kinetochores appeared to display proper co-orientation. However, when both Xs were located on the same half spindle their kinetochores appeared to be oriented in the same direction. Thus, the prometaphase movement of achiasmate chromosomes is a congression-like process in which the two homologs undergo both separation and rejoining events that result in the either loss or establishment of proper kinetochore co-orientation. During this period of dynamic chromosome movement, the achiasmate homologs were connected by heterochromatic threads that can span large distances relative to the length of the developing spindle. Additionally, the passenger complex proteins Incenp and Aurora B appeared to localize to these heterochromatic threads. We propose that these threads assist in the rejoining of homologs and the congression of the migrating achiasmate homologs back to the main chromosomal mass prior to metaphase arrest.

  13. Meiotic recombination, synapsis, meiotic inactivation and sperm aneuploidy in a chromosome 1 inversion carrier.

    Science.gov (United States)

    Kirkpatrick, Gordon; Chow, Victor; Ma, Sai

    2012-01-01

    Disrupted meiotic behaviour of inversion carriers may be responsible for suboptimal sperm parameters in these carriers. This study investigated meiotic recombination, synapsis, transcriptional silencing and chromosome segregation effects in a pericentric inv(1) carrier. Recombination (MLH1), synapsis (SYCP1, SYCP3) and transcriptional inactivation (γH2AX, BRCA1) were examined by fluorescence immunostaining. Chromosome specific rates of recombination were determined by fluorescence in-situ hybridization. Furthermore, testicular sperm was examined for aneuploidy and segregation of the inv(1). Our findings showed that global recombination rates were similar to controls. Recombination on the inv(1) and the sex chromosomes were reduced. The inv(1) associated with the XY body in 43.4% of cells, in which XY recombination was disproportionately absent, and 94.3% of cells displayed asynapsed regions which displayed meiotic silencing regardless of their association with the XY body. Furthermore, a low frequency of chromosomal imbalance was observed in spermatozoa (3.4%). Our results suggest that certain inversion carriers may display unimpaired global recombination and impaired recombination on the involved and the sex chromosomes during meiosis. Asynapsis or inversion-loop formation in the inverted region may be responsible for impaired spermatogenesis and may prevent sperm-chromosome imbalance.

  14. Kinetochore-independent chromosome poleward movement during anaphase of meiosis II in mouse eggs.

    Directory of Open Access Journals (Sweden)

    Manqi Deng

    Full Text Available Kinetochores are considered to be the key structures that physically connect spindle microtubules to the chromosomes and play an important role in chromosome segregation during mitosis. Due to different mechanisms of spindle assembly between centrosome-containing mitotic cells and acentrosomal meiotic oocytes, it is unclear how a meiotic spindle generates the poleward forces to drive two rounds of meiotic chromosome segregation to achieve genome haploidization. We took advantage of the fact that DNA beads are able to induce bipolar spindle formation without kinetochores and studied the behavior of DNA beads in the induced spindle in mouse eggs during meiosis II. Interestingly, DNA beads underwent poleward movements that were similar in timing and speed to the meiotic chromosomes, although all the beads moved together to the same spindle pole. Disruption of dynein function abolished the poleward movements of DNA beads but not of the meiotic chromosomes, suggesting the existence of different dynein-dependent and dynein-independent force generation mechanisms for the chromosome poleward movement, and the latter may be dependent on the presence of kinetochores. Consistent with the observed DNA bead poleward movement, sperm haploid chromatin (which also induced bipolar spindle formation after injection to a metaphase egg without forming detectable kinetochore structures also underwent similar poleward movement at anaphase as DNA beads. The results suggest that in the chromatin-induced meiotic spindles, kinetochore attachments to spindle microtubules are not absolutely required for chromatin poleward movements at anaphase.

  15. Structural organization of very small chromosomes: study on a single-celled evolutionary distant eukaryote Giardia intestinalis.

    Science.gov (United States)

    Tůmová, Pavla; Uzlíková, Magdalena; Wanner, Gerhard; Nohýnková, Eva

    2015-03-01

    During mitotic prophase, chromosomes of the pathogenic unicellular eukaryote Giardia intestinalis condense in each of the cell's two nuclei. In this study, Giardia chromosomes were investigated using light microscopy, high-resolution field emission scanning electron microscopy, and in situ hybridization. For the first time, we describe the overall morphology, condensation stages, and mitotic segregation of these chromosomes. Despite the absence of several genes involved in the cohesion and condensation pathways in the Giardia genome, we observed chromatin organization similar to those found in eukaryotes, i.e., 10-nm nucleosomal fibrils, 30-nm fibrils coiled to chromomeres or in parallel arrangements, and closely aligned sister chromatids. DNA molecules of Giardia terminate with telomeric repeats that we visualized on each of the four chromatid endings of metaphase chromosomes. Giardia chromosomes lack primary and secondary constrictions, thus preventing their classification based on the position of the centromere. The anaphase poleward segregation of sister chromatids is atypical in orientation and tends to generate lagging chromatids between daughter nuclei. In the Giardia genome database, we identified two putative members of the kleisin family thought to be responsible for condensin ring establishment. Thus far, Giardia chromosomes (300 nm to 1.5 μm) are the smallest chromosomes that were analyzed at the ultrastructural level. This study complements the existing molecular and sequencing data on Giardia chromosomes with cytological and ultrastructural information.

  16. Speech Segregation based on Binary Classification

    Science.gov (United States)

    2016-07-15

    other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a...to the adoption of the ideal ratio mask (IRM). A subsequent listening evaluation shows increased intelligibility in noise for human listeners...15. SUBJECT TERMS Binary classification, time-frequency masking, supervised speech segregation, speech intelligibility , room reverberation 16

  17. Segregation effects in DEEP2 galaxy groups

    Science.gov (United States)

    Nascimento, R. S.; Ribeiro, A. L. B.; Lopes, P. A. A.

    2016-09-01

    We investigate segregation phenomena in galaxy groups in the range of 0.2 low(z ≤ 0.6) and high (z > 0.6) redshift groups. Assuming that the color index (U - B)0 can be used as a proxy for the galaxy type, we found that the fraction of blue (star-forming) objects is higher in the high-z sample, with blue objects being dominant at MB > -19.5 for both samples, and red objects being dominant at MB low-z sample. Also, the radial variation of the red fraction indicates that there are more red objects with R low-z sample than in the high-z sample. Our analysis indicates statistical evidence of kinematic segregation, at the 99% c.l., for the low-z sample: redder and brighter galaxies present lower velocity dispersions than bluer and fainter ones. We also find a weaker evidence for spatial segregation between red and blue objects, at the 70% c.l. The analysis of the high-z sample reveals a different result: red and blue galaxies have velocity dispersion distributions not statistically distinct, although redder objects are more concentrated than the bluer ones at the 95% c.l. From the comparison of blue/red and bright/faint fractions, and considering the approximate lookback timescale between the two samples (˜3 Gyr), our results are consistent with a scenario where bright red galaxies had time to reach energy equipartition, while faint blue/red galaxies in the outskirts infall to the inner parts of the groups, thus reducing spatial segregation from z ˜ 0.8 to z ˜ 0.4.

  18. Effects of container geometry on granular segregation pattern

    Institute of Scientific and Technical Information of China (English)

    Hu Mao-Bin; Kong Xiang-Zhao; Wu Qing-Song; Wu Yong-Hong

    2005-01-01

    In a set of vibrating quasi-two-dimensional containers with the right-hand sidewall bent inward, three new segregation patterns have been identified experimentally including a Two-Side segregation Pattern, a Left-hand Side segregation Pattern and a pattern where big particles aggregate to the upper left part of the container. In a container with small bending degree, either the two-side segregation pattern or the left-hand side segregation pattern is stable, which is determined by the initial distribution of particles.

  19. Segregation effects in DEEP2 galaxy groups

    CERN Document Server

    Nascimento, Raquel S; Lopes, Paulo A A

    2016-01-01

    We investigate segregation phenomena in galaxy groups in the range of $0.20.6$) redshift groups. Assuming that the color index ${(U-B)_0}$ can be used as a proxy for the galaxy type, we found that the fraction of blue (star-forming) objects is higher in the high-z sample, with blue objects being dominant at $M_{B}>-19.5$ for both samples, and red objects being dominant at $M_{B}<-19.5$ only for the low-z sample. Also, the radial variation of the red fraction indicates that there are more red objects with $Rsegregation, at the 99%c.l., for the low-z sample: redder and brighter galaxies present lower velocity dispersions than bluer and fainter ones. We also find a weaker evidence for spatial segregation between red and blue objects, at the 70%c.l. The analysis of the high-z sample reveals a different result: red and blue galaxies have velocity dispersion distributions not statistically distinc...

  20. Integration and segregation in auditory scene analysis

    Science.gov (United States)

    Sussman, Elyse S.

    2005-03-01

    Assessment of the neural correlates of auditory scene analysis, using an index of sound change detection that does not require the listener to attend to the sounds [a component of event-related brain potentials called the mismatch negativity (MMN)], has previously demonstrated that segregation processes can occur without attention focused on the sounds and that within-stream contextual factors influence how sound elements are integrated and represented in auditory memory. The current study investigated the relationship between the segregation and integration processes when they were called upon to function together. The pattern of MMN results showed that the integration of sound elements within a sound stream occurred after the segregation of sounds into independent streams and, further, that the individual streams were subject to contextual effects. These results are consistent with a view of auditory processing that suggests that the auditory scene is rapidly organized into distinct streams and the integration of sequential elements to perceptual units takes place on the already formed streams. This would allow for the flexibility required to identify changing within-stream sound patterns, needed to appreciate music or comprehend speech..

  1. Implementing spatial segregation measures in R.

    Directory of Open Access Journals (Sweden)

    Seong-Yun Hong

    Full Text Available Reliable and accurate estimation of residential segregation between population groups is important for understanding the extent of social cohesion and integration in our society. Although there have been considerable methodological advances in the measurement of segregation over the last several decades, the recently developed measures have not been widely used in the literature, in part due to their complex calculation. To address this problem, we have implemented several newly proposed segregation indices in R, an open source software environment for statistical computing and graphics, as a package called seg. Although there are already a few standalone applications and add-on packages that provide access to similar methods, our implementation has a number of advantages over the existing tools. First, our implementation is flexible in the sense that it provides detailed control over the calculation process with a wide range of input parameters. Most of the parameters have carefully chosen defaults, which perform acceptably in many situations, so less experienced users can also use the implemented functions without too much difficulty. Second, there is no need to export results to other software programs for further analysis. We provide coercion methods that enable the transformation of our output classes into general R classes, so the user can use thousands of standard and modern statistical techniques, which are already available in R, for the post-processing of the results. Third, our implementation does not require commercial software to operate, so it is accessible to a wider group of people.

  2. Audiovisual segregation in cochlear implant users.

    Directory of Open Access Journals (Sweden)

    Simon Landry

    Full Text Available It has traditionally been assumed that cochlear implant users de facto perform atypically in audiovisual tasks. However, a recent study that combined an auditory task with visual distractors suggests that only those cochlear implant users that are not proficient at recognizing speech sounds might show abnormal audiovisual interactions. The present study aims at reinforcing this notion by investigating the audiovisual segregation abilities of cochlear implant users in a visual task with auditory distractors. Speechreading was assessed in two groups of cochlear implant users (proficient and non-proficient at sound recognition, as well as in normal controls. A visual speech recognition task (i.e. speechreading was administered either in silence or in combination with three types of auditory distractors: i noise ii reverse speech sound and iii non-altered speech sound. Cochlear implant users proficient at speech recognition performed like normal controls in all conditions, whereas non-proficient users showed significantly different audiovisual segregation patterns in both speech conditions. These results confirm that normal-like audiovisual segregation is possible in highly skilled cochlear implant users and, consequently, that proficient and non-proficient CI users cannot be lumped into a single group. This important feature must be taken into account in further studies of audiovisual interactions in cochlear implant users.

  3. Structural rearrangements of chromosome 15 satellites resulting in Prader-Willi syndrome suggest a complex mechanism for uniparental disomy

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fijel, S.; Gunter, K.; Olson, S. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1994-09-01

    We report two cases of PWS in which there was abnormal meiosis I segregation of chromosome 15 following a rare translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and an apparent meiotic recombination in the unstable region of 15q11.2. PWS and normal appearing chromosomes in case one prompted a chromosome 15 origin analysis. PCR analysis indicated maternal isodisomy for the long arm of chromosome. However, only one chromosome 15 had short arm heteromorphisms consistent with either paternal or maternal inheritance. VNTR DNA analysis and heteromorphism data suggest that a maternal de novo translocation between chromosome 14 and 15 occurred prior to meiosis I. This was followed by recombination between D15Z1 and D15S11 and subsequent meiosis I nondisjunction. Proband and maternal karyotype display a distamycin A-DAPI positive region on the chromosome 14 homolog involved in the translocation. Fluorescent in situ hybridization (FISH) analyses of ONCOR probes D15S11, SNRPN, D15S11 and GABRB 3 were normal, consistent with the molecular data. Case two received a Robertsonian translocation t(14;15)(p13;p13) of maternal origin. Chromosome analysis revealed a meiosis I error producing UPD. FISH analysis of the proband and parents showed normal hybridization of ONCOR probes D15Z1, D15S11, SNRPN, D15S10 and GABRB3. In both cases the PWS probands received a structurally altered chromosome 15 that had rearranged with chromosome 14 prior to meiosis. If proper meiotic segregation is dependent on the resolution of chiasmata and/or the binding to chromosome-specific spindle fibers, then it may be possible that rearrangements of pericentric or unstable regions of the genome disrupt normal disjunction and lead to uniparental disomy.

  4. Dynamical scenarios for chromosome bi-orientation.

    Science.gov (United States)

    Zhang, Tongli; Oliveira, Raquel A; Schmierer, Bernhard; Novák, Béla

    2013-06-18

    Chromosome bi-orientation at the metaphase spindle is essential for precise segregation of the genetic material. The process is error-prone, and error-correction mechanisms exist to switch misaligned chromosomes to the correct, bi-oriented configuration. Here, we analyze several possible dynamical scenarios to explore how cells might achieve correct bi-orientation in an efficient and robust manner. We first illustrate that tension-mediated feedback between the sister kinetochores can give rise to a bistable switch, which allows robust distinction between a loose attachment with low tension and a strong attachment with high tension. However, this mechanism has difficulties in explaining how bi-orientation is initiated starting from unattached kinetochores. We propose four possible mechanisms to overcome this problem (exploiting molecular noise; allowing an efficient attachment of kinetochores already in the absence of tension; a trial-and-error oscillation; and a stochastic bistable switch), and assess their impact on the bi-orientation process. Based on our results and supported by experimental data, we put forward a trial-and-error oscillation and a stochastic bistable switch as two elegant mechanisms with the potential to promote bi-orientation both efficiently and robustly.

  5. Spatiotemporal choreography of chromosome and megaplasmids in the Sinorhizobium meliloti cell cycle.

    Science.gov (United States)

    Frage, Benjamin; Döhlemann, Johannes; Robledo, Marta; Lucena, Daniella; Sobetzko, Patrick; Graumann, Peter L; Becker, Anke

    2016-06-01

    A considerable share of bacterial species maintains multipartite genomes. Precise coordination of genome replication and segregation with cell growth and division is vital for proliferation of these bacteria. The α-proteobacterium Sinorhizobium meliloti possesses a tripartite genome composed of one chromosome and the megaplasmids pSymA and pSymB. Here, we investigated the spatiotemporal pattern of segregation of these S. meliloti replicons at single cell level. Duplication of chromosomal and megaplasmid origins of replication occurred spatially and temporally separated, and only once per cell cycle. Tracking of FROS (fluorescent repressor operator system)-labelled origins revealed a strict temporal order of segregation events commencing with the chromosome followed by pSymA and then by pSymB. The repA2B2C2 region derived from pSymA was sufficient to confer the spatiotemporal behaviour of this megaplasmid to a small plasmid. Altering activity of the ubiquitous prokaryotic replication initiator DnaA, either positively or negatively, resulted in an increase in replication initiation events or G1 arrest of the chromosome only. This suggests that interference with DnaA activity does not affect replication initiation control of the megaplasmids.

  6. Genetic dosage and position effect of small supernumerary marker chromosome (sSMC) in human sperm nuclei in infertile male patient.

    Science.gov (United States)

    Olszewska, Marta; Wanowska, Elzbieta; Kishore, Archana; Huleyuk, Nataliya; Georgiadis, Andrew P; Yatsenko, Alexander N; Mikula, Mariya; Zastavna, Danuta; Wiland, Ewa; Kurpisz, Maciej

    2015-11-30

    Chromosomes occupy specific distinct areas in the nucleus of the sperm cell that may be altered in males with disrupted spermatogenesis. Here, we present alterations in the positioning of the human chromosomes 15, 18, X and Y between spermatozoa with the small supernumerary marker chromosome (sSMC; sSMC(+)) and spermatozoa with normal chromosome complement (sSMC(-)), for the first time described in the same ejaculate of an infertile, phenotypically normal male patient. Using classical and confocal fluorescent microscopy, the nuclear colocalization of chromosomes 15 and sSMC was analyzed. The molecular cytogenetic characteristics of sSMC delineated the karyotype as 47,XY,+der(15)(pter->p11.2::q11.1->q11.2::p11.2->pter)mat. Analysis of meiotic segregation showed a 1:1 ratio of sSMC(+) to sSMC(-) spermatozoa, while evaluation of sperm aneuploidy status indicated an increased level of chromosome 13, 18, 21 and 22 disomy, up to 7 × (2.7 - 15.1). Sperm chromatin integrity assessment did not reveal any increase in deprotamination in the patient's sperm chromatin. Importantly, we found significant repositioning of chromosomes X and Y towards the nuclear periphery, where both chromosomes were localized in close proximity to the sSMC. This suggests the possible influence of sSMC/XY colocalization on meiotic chromosome division, resulting in abnormal chromosome segregation, and leading to male infertility in the patient.

  7. Mutiscale Modeling of Segregation in Granular Flows

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jin [Iowa State Univ., Ames, IA (United States)

    2007-01-01

    Modeling and simulation of segregation phenomena in granular flows are investigated. Computational models at different scales ranging from particle level (microscale) to continuum level (macroscale) are employed in order to determine the important microscale physics relevant to macroscale modeling. The capability of a multi-fluid model to capture segregation caused by density difference is demonstrated by simulating grain-chaff biomass flows in a laboratory-scale air column and in a combine harvester. The multi-fluid model treats gas and solid phases as interpenetrating continua in an Eulerian frame. This model is further improved by incorporating particle rotation using kinetic theory for rapid granular flow of slightly frictional spheres. A simplified model is implemented without changing the current kinetic theory framework by introducing an effective coefficient of restitution to account for additional energy dissipation due to frictional collisions. The accuracy of predicting segregation rate in a gas-fluidized bed is improved by the implementation. This result indicates that particle rotation is important microscopic physics to be incorporated into the hydrodynamic model. Segregation of a large particle in a dense granular bed of small particles under vertical. vibration is studied using molecular dynamics simulations. Wall friction is identified as a necessary condition for the segregation. Large-scale force networks bearing larger-than-average forces are found with the presence of wall friction. The role of force networks in assisting rising of the large particle is analyzed. Single-point force distribution and two-point spatial force correlation are computed. The results show the heterogeneity of forces and a short-range correlation. The short correlation length implies that even dense granular flows may admit local constitutive relations. A modified minimum spanning tree (MST) algorithm is developed to asymptotically recover the force statistics in the

  8. The role of chromosome missegregation in cancer development: a theoretical approach using agent-based modelling.

    Directory of Open Access Journals (Sweden)

    Arturo Araujo

    Full Text Available Many cancers are aneuploid. However, the precise role that chromosomal instability plays in the development of cancer and in the response of tumours to treatment is still hotly debated. Here, to explore this question from a theoretical standpoint we have developed an agent-based model of tissue homeostasis in which to test the likely effects of whole chromosome mis-segregation during cancer development. In stochastic simulations, chromosome mis-segregation events at cell division lead to the generation of a diverse population of aneuploid clones that over time exhibit hyperplastic growth. Significantly, the course of cancer evolution depends on genetic linkage, as the structure of chromosomes lost or gained through mis-segregation events and the level of genetic instability function in tandem to determine the trajectory of cancer evolution. As a result, simulated cancers differ in their level of genetic stability and in their growth rates. We used this system to investigate the consequences of these differences in tumour heterogeneity for anti-cancer therapies based on surgery and anti-mitotic drugs that selectively target proliferating cells. As expected, simulated treatments induce a transient delay in tumour growth, and reveal a significant difference in the efficacy of different therapy regimes in treating genetically stable and unstable tumours. These data support clinical observations in which a poor prognosis is correlated with a high level of chromosome mis-segregation. However, stochastic simulations run in parallel also exhibit a wide range of behaviours, and the response of individual simulations (equivalent to single tumours to anti-cancer therapy prove extremely variable. The model therefore highlights the difficulties of predicting the outcome of a given anti-cancer treatment, even in cases in which it is possible to determine the genotype of the entire set of cells within the developing tumour.

  9. Can corruption of chromosome cohesion create a conduit to cancer?

    Science.gov (United States)

    Xu, Huiling; Tomaszewski, Jonathan M; McKay, Michael J

    2011-03-01

    Cohesin is a conserved multisubunit protein complex with diverse cellular roles, making key contributions to the coordination of chromosome segregation, the DNA damage response and chromatin regulation by epigenetic mechanisms. Much has been learned in recent years about the roles of cohesin in a physiological context, whereas its potential and emerging role in tumour initiation and/or progression has received relatively little attention. In this Opinion article we examine how cohesin deregulation could contribute to cancer development on the basis of its physiological roles.

  10. Super-resolution imaging of Escherichia coli nucleoids reveals highly structured and asymmetric segregation during fast growth.

    Science.gov (United States)

    Spahn, Christoph; Endesfelder, Ulrike; Heilemann, Mike

    2014-03-01

    Bacterial replication and chromosome segregation are highly organized both in space and in time. However, spatial analysis is hampered by the resolution limit of conventional fluorescence microscopy. In this study, we incubate rapidly-growing Escherichia coli with 5-ethynyl-2'-deoxyuridine (EdU), label the resulting EdU-DNA with photoswitchable fluorophores, and image incorporated molecules with an average experimental precision of 13 nm. During the segregation process, nucleoids develop highly-defined and cell-cycle dependent hetero-structures, which contain discrete DNA fibers with diameters far below the diffraction limit. Strikingly, these structures appear temporally shifted between sister chromosomes, an asymmetry which accumulates for ongoing replication rounds. Moreover, nucleoid positioning and expansion along the bacterial length axis fit into an elongation-mediated segregation model in fast growing E. coli cultures. This is supported by close proximity of the nucleoids to the bacterial plasma membrane, the nature of the observed hetero-structures and recently found interactions of membrane-associated proteins with DNA.

  11. "Chromosome": a knowledge-based system for the chromosome classification.

    Science.gov (United States)

    Ramstein, G; Bernadet, M

    1993-01-01

    Chromosome, a knowledge-based analysis system has been designed for the classification of human chromosomes. Its aim is to perform an optimal classification by driving a tool box containing the procedures of image processing, pattern recognition and classification. This paper presents the general architecture of Chromosome, based on a multiagent system generator. The image processing tool box is described from the met aphasic enhancement to the fine classification. Emphasis is then put on the knowledge base intended for the chromosome recognition. The global classification process is also presented, showing how Chromosome proceeds to classify a given chromosome. Finally, we discuss further extensions of the system for the karyotype building.

  12. FtsK-dependent dimer resolution on multiple chromosomes in the pathogen Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Marie-Eve Val

    Full Text Available Unlike most bacteria, Vibrio cholerae harbors two distinct, nonhomologous circular chromosomes (chromosome I and II. Many features of chromosome II are plasmid-like, which raised questions concerning its chromosomal nature. Plasmid replication and segregation are generally not coordinated with the bacterial cell cycle, further calling into question the mechanisms ensuring the synchronous management of chromosome I and II. Maintenance of circular replicons requires the resolution of dimers created by homologous recombination events. In Escherichia coli, chromosome dimers are resolved by the addition of a crossover at a specific site, dif, by two tyrosine recombinases, XerC and XerD. The process is coordinated with cell division through the activity of a DNA translocase, FtsK. Many E. coli plasmids also use XerCD for dimer resolution. However, the process is FtsK-independent. The two chromosomes of the V. cholerae N16961 strain carry divergent dimer resolution sites, dif1 and dif2. Here, we show that V. cholerae FtsK controls the addition of a crossover at dif1 and dif2 by a common pair of Xer recombinases. In addition, we show that specific DNA motifs dictate its orientation of translocation, the distribution of these motifs on chromosome I and chromosome II supporting the idea that FtsK translocation serves to bring together the resolution sites carried by a dimer at the time of cell division. Taken together, these results suggest that the same FtsK-dependent mechanism coordinates dimer resolution with cell division for each of the two V. cholerae chromosomes. Chromosome II dimer resolution thus stands as a bona fide chromosomal process.

  13. Chromosome numbers in Bromeliaceae

    Directory of Open Access Journals (Sweden)

    Cotias-de-Oliveira Ana Lúcia Pires

    2000-01-01

    Full Text Available The present study reports chromosome numbers of 17 species of Bromeliaceae, belonging to the genera Encholirium, Bromelia, Orthophytum, Hohenbergia, Billbergia, Neoglaziovia, Aechmea, Cryptanthus and Ananas. Most species present 2n = 50, however, Bromelia laciniosa, Orthophytum burle-marxii and O. maracasense are polyploids with 2n = 150, 2n = 100 and 2n = 150, respectively, while for Cryptanthus bahianus, 2n = 34 + 1-4B. B chromosomes were observed in Bromelia plumieri and Hohenbergia aff. utriculosa. The chromosome number of all species was determined for the first time, except for Billbergia chlorosticta and Cryptanthus bahianus. Our data supports the hypothesis of a basic number of x = 25 for the Bromeliaceae family and decreasing aneuploidy in the genus Cryptanthus.

  14. Those amazing dinoflagellate chromosomes

    Institute of Scientific and Technical Information of China (English)

    PETER J RIZZO

    2003-01-01

    Dinoflagellates are a very large and diverse group of eukaryotic algae that play a major role in aquatic food webs of both fresh water and marine habitats. Moreover, the toxic members of this group pose a health threat in the form of red tides. Finally, dinoflagellates are of great evolutionary importance,because of their taxonomic position, and their unusual chromosome structure and composition. While the cytoplasm of dinoflagellates is typically eukaryotic, the nucleus is unique when compared to the nucleus of other eukaryotes. More specifically, while the chromosomes of all other eukaryotes contain histones,dinoflagellate chromosomes lack histones completely. There are no known exceptions to this observation: all dinoflagellates lack histones, and all other eukaryotes contain histones. Nevertheless, dinoflagellates remain a relatively unstudied group of eukaryotes.

  15. Analysis of Recombination and Chromosome Structure during Yeast Meiosis.

    Science.gov (United States)

    Börner, G Valentin; Cha, Rita S

    2015-11-02

    Meiosis is a diploid-specific differentiation program that consists of a single round of genome duplication followed by two rounds of chromosome segregation. These events result in halving of the genetic complement, which is a requirement for formation of haploid reproductive cells (i.e., spores in yeast and gametes in animals and plants). During meiosis I, homologous maternal and paternal chromosomes (homologs) pair and separate, whereas sister chromatids remain connected at the centromeres and separate during the second meiotic division. In most organisms, accurate homolog disjunction requires crossovers, which are formed as products of meiotic recombination. For the past two decades, studies of yeast meiosis have provided invaluable insights into evolutionarily conserved mechanisms of meiosis.

  16. Amitozyn Impairs Chromosome Segregation and Induces Apoptosis via Mitotic Checkpoint Activation

    Science.gov (United States)

    Potopalsky, Anatoly I.; Chroboczek, Jadwiga; Tcherniuk, Sergey O.

    2013-01-01

    Amitozyn (Am) is a semi-synthetic drug produced by the alkylation of major celandine (Chelidonium majus L.) alkaloids with the organophosphorous compound N,N’N’-triethylenethiophosphoramide (ThioTEPA). We show here that the treatment of living cells with Am reversibly perturbs the microtubule cytoskeleton, provoking a dose-dependent cell arrest in the M phase. Am changed the dynamics of tubulin polymerization in vitro, promoted the appearance of aberrant mitotic phenotypes in HeLa cells and induced apoptosis by the activation of caspase-9, caspase-3 and PARP, without inducing DNA breaks. Am treatment of HeLa cells induced changes in the phosphorylation of the growth suppressor pRb that coincided with maximum mitotic index. The dose-dependent and reversible anti-proliferative effect of Am was observed in several transformed cell lines. Importantly, the drug was also efficient against multidrug-resistant, paclitaxel-resistant or p53-deficient cells. Our results thus open the way to further pre-clinical evaluation of Am. PMID:23505430

  17. Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Edyta Marcon

    2014-07-01

    Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  18. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation.

    Science.gov (United States)

    Marcon, Edyta; Ni, Zuyao; Pu, Shuye; Turinsky, Andrei L; Trimble, Sandra Smiley; Olsen, Jonathan B; Silverman-Gavrila, Rosalind; Silverman-Gavrila, Lorelei; Phanse, Sadhna; Guo, Hongbo; Zhong, Guoqing; Guo, Xinghua; Young, Peter; Bailey, Swneke; Roudeva, Denitza; Zhao, Dorothy; Hewel, Johannes; Li, Joyce; Gräslund, Susanne; Paduch, Marcin; Kossiakoff, Anthony A; Lupien, Mathieu; Emili, Andrew; Wodak, Shoshana J; Greenblatt, Jack

    2014-07-10

    Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision) network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  19. A role for the fission yeast Rqh1 helicase in chromosome segregation

    DEFF Research Database (Denmark)

    Win, Thein Z; Mankouri, Hocine W; Hickson, Ian D;

    2005-01-01

    Schizosaccharomyces pombe Rqh1 protein is a member of the RecQ DNA helicase family. Members of this protein family are mutated in several human genome instability syndromes, including Bloom, Werner and Rothmund-Thomson syndromes. RecQ helicases participate in recombination repair of stalled...

  20. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Science.gov (United States)

    Mengoli, Valentina; Bucciarelli, Elisabetta; Lattao, Ramona; Piergentili, Roberto; Gatti, Maurizio; Bonaccorsi, Silvia

    2014-10-01

    Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on slight differences

  1. The analysis of mutant alleles of different strength reveals multiple functions of topoisomerase 2 in regulation of Drosophila chromosome structure.

    Directory of Open Access Journals (Sweden)

    Valentina Mengoli

    2014-10-01

    Full Text Available Topoisomerase II is a major component of mitotic chromosomes but its role in the assembly and structural maintenance of chromosomes is rather controversial, as different chromosomal phenotypes have been observed in various organisms and in different studies on the same organism. In contrast to vertebrates that harbor two partially redundant Topo II isoforms, Drosophila and yeasts have a single Topo II enzyme. In addition, fly chromosomes, unlike those of yeast, are morphologically comparable to vertebrate chromosomes. Thus, Drosophila is a highly suitable system to address the role of Topo II in the assembly and structural maintenance of chromosomes. Here we show that modulation of Top2 function in living flies by means of mutant alleles of different strength and in vivo RNAi results in multiple cytological phenotypes. In weak Top2 mutants, meiotic chromosomes of males exhibit strong morphological abnormalities and dramatic segregation defects, while mitotic chromosomes of larval brain cells are not affected. In mutants of moderate strength, mitotic chromosome organization is normal, but anaphases display frequent chromatin bridges that result in chromosome breaks and rearrangements involving specific regions of the Y chromosome and 3L heterochromatin. Severe Top2 depletion resulted in many aneuploid and polyploid mitotic metaphases with poorly condensed heterochromatin and broken chromosomes. Finally, in the almost complete absence of Top2, mitosis in larval brains was virtually suppressed and in the rare mitotic figures observed chromosome morphology was disrupted. These results indicate that different residual levels of Top2 in mutant cells can result in different chromosomal phenotypes, and that the effect of a strong Top2 depletion can mask the effects of milder Top2 reductions. Thus, our results suggest that the previously observed discrepancies in the chromosomal phenotypes elicited by Topo II downregulation in vertebrates might depend on

  2. Somatic pairing, endomitosis and chromosome aberrations in snakes (Viperidae and Colubridae

    Directory of Open Access Journals (Sweden)

    Beçak Maria Luiza

    2003-01-01

    Full Text Available The positioning of macrochromosomes of Bothrops jararaca and Bothrops insularis (Viperidae was studied in undistorted radial metaphases of uncultured cells (spermatogonia and oogonia not subjected to spindle inhibitors. Colchicinized metaphases from uncultured (spleen and intestine and cultured tissues (blood were also analyzed. We report two antagonic non-random chromosome arrangements in untreated premeiotic cells: the parallel configuration with homologue chromosomes associated side by side in the metaphase plate and the antiparallel configuration having homologue chromosomes with antipolar distribution in the metaphase ring. The antiparallel aspect also appeared in colchicinized cells. The spatial chromosome arrangement in both configurations is groupal size-dependent and maintained through meiosis. We also describe, in untreated gonia cells, endomitosis followed by reductional mitosis which restores the diploid number. In B. jararaca males we observed that some gonad regions present changes in the meiotic mechanism. In this case, endoreduplicated cells segregate the diplochromosomes to opposite poles forming directly endoreduplicated second metaphases of meiosis with the suppression of first meiosis. By a successive division, these cells form nuclei with one set of chromosomes. Chromosome doubling in oogonia is known in hybrid species and in parthenogenetic salamanders and lizards. This species also presented chromosome rearrangements leading to aneuploidies in mitosis and meiosis. It is suggested that somatic pairing, endomitosis, meiotic alterations, and chromosomal aberrations can be correlated processes. Similar aspects of nuclei configurations, endomitosis and reductional mitosis were found in other Viperidae and Colubridae species.

  3. Loss of pRB causes centromere dysfunction and chromosomal instability.

    Science.gov (United States)

    Manning, Amity L; Longworth, Michelle S; Dyson, Nicholas J

    2010-07-01

    Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

  4. Evidence for a Xer/dif system for chromosome resolution in archaea.

    Directory of Open Access Journals (Sweden)

    Diego Cortez

    2010-10-01

    Full Text Available Homologous recombination events between circular chromosomes, occurring during or after replication, can generate dimers that need to be converted to monomers prior to their segregation at cell division. In Escherichia coli, chromosome dimers are converted to monomers by two paralogous site-specific tyrosine recombinases of the Xer family (XerC/D. The Xer recombinases act at a specific dif site located in the replication termination region, assisted by the cell division protein FtsK. This chromosome resolution system has been predicted in most Bacteria and further characterized for some species. Archaea have circular chromosomes and an active homologous recombination system and should therefore resolve chromosome dimers. Most archaea harbour a single homologue of bacterial XerC/D proteins (XerA, but not of FtsK. Therefore, the role of XerA in chromosome resolution was unclear. Here, we have identified dif-like sites in archaeal genomes by using a combination of modeling and comparative genomics approaches. These sites are systematically located in replication termination regions. We validated our in silico prediction by showing that the XerA protein of Pyrococcus abyssi specifically recombines plasmids containing the predicted dif site in vitro. In contrast to the bacterial system, XerA can recombine dif sites in the absence of protein partners. Whereas Archaea and Bacteria use a completely different set of proteins for chromosome replication, our data strongly suggest that XerA is most likely used for chromosome resolution in Archaea.

  5. Chromosomal rearrangements in cattle and pigs revealed by chromosome microdissection and chromosome painting

    Directory of Open Access Journals (Sweden)

    Yerle Martine

    2003-11-01

    Full Text Available Abstract A pericentric inversion of chromosome 4 in a boar, as well as a case of (2q-;5p+ translocation mosaicism in a bull were analysed by chromosome painting using probes generated by conventional microdissection. For the porcine inversion, probes specific for p arms and q arms were produced and hybridised simultaneously on metaphases of a heterozygote carrier. In the case of the bovine translocation, two whole chromosome probes (chromosome 5, and derived chromosome 5 were elaborated and hybridised independently on chromosomal preparations of the bull who was a carrier of the mosaic translocation. The impossibility of differentiating chromosomes 2 and der(2 from other chromosomes of the metaphases did not allow the production of painting probes for these chromosomes. For all experiments, the quality of painting was comparable to that usually observed with probes obtained from flow-sorted chromosomes. The results obtained allowed confirmation of the interpretations proposed with G-banding karyotype analyses. In the bovine case, however, the reciprocity of the translocation could not be proven. The results presented in this paper show the usefulness of the microdissection technique for characterising chromosomal rearrangements in species for which commercial probes are not available. They also confirmed that the main limiting factor of the technique is the quality of the chromosomal preparations, which does not allow the identification of target chromosomes or chromosome fragments in all cases.

  6. Association of condensin with chromosomes depends on DNA binding by its HEAT-repeat subunits.

    Science.gov (United States)

    Piazza, Ilaria; Rutkowska, Anna; Ori, Alessandro; Walczak, Marta; Metz, Jutta; Pelechano, Vicent; Beck, Martin; Haering, Christian H

    2014-06-01

    Condensin complexes have central roles in the three-dimensional organization of chromosomes during cell divisions, but how they interact with chromatin to promote chromosome segregation is largely unknown. Previous work has suggested that condensin, in addition to encircling chromatin fibers topologically within the ring-shaped structure formed by its SMC and kleisin subunits, contacts DNA directly. Here we describe the discovery of a binding domain for double-stranded DNA formed by the two HEAT-repeat subunits of the Saccharomyces cerevisiae condensin complex. From detailed mapping data of the interfaces between the HEAT-repeat and kleisin subunits, we generated condensin complexes that lack one of the HEAT-repeat subunits and consequently fail to associate with chromosomes in yeast and human cells. The finding that DNA binding by condensin's HEAT-repeat subunits stimulates the SMC ATPase activity suggests a multistep mechanism for the loading of condensin onto chromosomes.

  7. Msh2 deficiency leads to chromosomal abnormalities, centrosome amplification, and telomere capping defect

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yisong [ORNL; Liu, Yie [ORNL

    2006-01-01

    Msh2 is a key mammalian DNA mismatch repair (MMR) gene and mutations or deficiencies in mammalian Msh2 gene result in microsatellite instability (MSI+) and the development of cancer. Here, we report that primary mouse embryonic fibroblasts (MEFs) deficient in the murine MMR gene Msh2 (Msh2-/-) showed a significant increase in chromosome aneuploidy, centrosome amplification, and defective mitotic spindle organization and unequal chromosome segregation. Although Msh2-/- mouse tissues or primary MEFs had no apparent change in telomerase activity, telomere length, or recombination at telomeres, Msh2-/- MEFs showed an increase in chromosome end-to-end fusions or chromosome ends without detectable telomeric DNA. These data suggest that MSH2 helps to maintain genomic stability through the regulation of the centrosome and normal telomere capping in vivo and that defects in MMR can contribute to oncogenesis through multiple pathways.

  8. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

    Science.gov (United States)

    Murdoch, Brenda; Owen, Nichole; Stevense, Michelle; Smith, Helen; Nagaoka, So; Hassold, Terry; McKay, Michael; Xu, Huiling; Fu, Jun; Revenkova, Ekaterina; Jessberger, Rolf; Hunt, Patricia

    2013-01-01

    Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC) and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  9. Altered cohesin gene dosage affects Mammalian meiotic chromosome structure and behavior.

    Directory of Open Access Journals (Sweden)

    Brenda Murdoch

    Full Text Available Based on studies in mice and humans, cohesin loss from chromosomes during the period of protracted meiotic arrest appears to play a major role in chromosome segregation errors during female meiosis. In mice, mutations in meiosis-specific cohesin genes cause meiotic disturbances and infertility. However, the more clinically relevant situation, heterozygosity for mutations in these genes, has not been evaluated. We report here evidence from the mouse that partial loss of gene function for either Smc1b or Rec8 causes perturbations in the formation of the synaptonemal complex (SC and affects both synapsis and recombination between homologs during meiotic prophase. Importantly, these defects increase the frequency of chromosomally abnormal eggs in the adult female. These findings have important implications for humans: they suggest that women who carry mutations or variants that affect cohesin function have an elevated risk of aneuploid pregnancies and may even be at increased risk of transmitting structural chromosome abnormalities.

  10. Chromosomal rearrangement interferes with meiotic X chromosome inactivation

    OpenAIRE

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-01-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X–autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencin...

  11. Isothermal Gravitational Segregation: Algorithms and Specifications

    DEFF Research Database (Denmark)

    Halldórsson, Snorri; Stenby, Erling Halfdan

    2000-01-01

    New algorithms for calculating the isothermal equilibrium state of reservoir fluids under the influence of gravity are presented. Two types of specifications are considered: the specification of pressure and composition at a reference depth; and the specification of the total overall content...... of the reservoir, along with the reservoir geometry. It is shown how both types of calculations can be performed in an efficient and robust manner using volume-based thermodynamics. The new method makes it possible to evaluate the influence of reservoir geometry and gravity segregation on the hydrocarbon reserves...

  12. Computing the complexity for Schelling segregation models

    Science.gov (United States)

    Gerhold, Stefan; Glebsky, Lev; Schneider, Carsten; Weiss, Howard; Zimmermann, Burkhard

    2008-12-01

    The Schelling segregation models are "agent based" population models, where individual members of the population (agents) interact directly with other agents and move in space and time. In this note we study one-dimensional Schelling population models as finite dynamical systems. We define a natural notion of entropy which measures the complexity of the family of these dynamical systems. The entropy counts the asymptotic growth rate of the number of limit states. We find formulas and deduce precise asymptotics for the number of limit states, which enable us to explicitly compute the entropy.

  13. ParABS system in chromosome partitioning in the bacterium Myxococcus xanthus.

    Science.gov (United States)

    Iniesta, Antonio A

    2014-01-01

    Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster.

  14. ParABS system in chromosome partitioning in the bacterium Myxococcus xanthus.

    Directory of Open Access Journals (Sweden)

    Antonio A Iniesta

    Full Text Available Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster.

  15. Chromosomal stickiness and related meiotic irregularities in Inula racemosa - a critically endangered medicinal herb of North Western Himalayas

    Directory of Open Access Journals (Sweden)

    Peerzada Arshid Shabir

    2013-07-01

    Full Text Available Background: The species Inula racemosa, a rare species of Kashmir Himalaya, has been included in the list of endangered species of India. In the present study, we aimed to make a more formal quantitative analysis of the fertility of I. racemosa, wild as well as transplanted populations, using a meiotic behaviour analysis and pollen viability test. Materials and Methods: Inflorescences at an ideal stage for meiotic study were collected and fixed in acetic ethanol (1:3 for 24 h and stored in 70% alcohol under refrigeration at 4˚C until use. For slide preparation the anthers were squashed in 2% acetocarmine. Results: The present study revealed a peculiar chromosomal stickiness and formation of interbivalent chromatin connections among 2-4 bivalents. This stickiness of chromosomes along with interbivalent chromatin connections impairs the correct segregation of chromosomes, as a result single and double chromosomal bridges of different thickness, different number of lagging chromosomes, unequal separation, and multipolarity were continuously observed from anaphase I to microspore stage. Consequent to stickiness and associated meiotic abnormalities, the pollen grains varied greatly in size, individuals show 24.05-38.83% pollen sterility. Conclusion: The presence of sticky chromosomes in I. racemosa impairs the correct segregation during anaphase which compromises the pollen viability of the species. Although the percentage of pollen sterility was not completely concord to the high rates of observed chromosomal abnormalities but the findings can aid in the successful conservation and management of the species.

  16. Segregation, choice based letting and social housing: How housing policy can affect the segregation process

    NARCIS (Netherlands)

    Van Ham, M.; Manley, D.

    2012-01-01

    In this chapter we investigate the process of ethnic minority segregation in English social housing. Successive governments have expressed a commitment to the con-tradictory aims of providing greater choice – through the introduction of choice based letting – for households accessing an increasingly

  17. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli;

    2014-01-01

    Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...

  18. Chromosome Variations And Human Behavior

    Science.gov (United States)

    Soudek, D.

    1974-01-01

    Article focused on the science of cytogenetics, which studied the transmission of the units of heredity called chromosomes, and considered the advantage of proper diagnosis of genetic diseases, treated on the chromosomal level. (Author/RK)

  19. Ring chromosome 13

    DEFF Research Database (Denmark)

    Brandt, C A; Hertz, Jens Michael; Petersen, M B;

    1992-01-01

    A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...

  20. Chromosomes, cancer and radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Samouhos, E.

    1983-08-01

    Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available.

  1. The Y Chromosome

    Science.gov (United States)

    Offner, Susan

    2010-01-01

    The Y chromosome is of great interest to students and can be used to teach about many important biological concepts in addition to sex determination. This paper discusses mutation, recombination, mammalian sex determination, sex determination in general, and the evolution of sex determination in mammals. It includes a student activity that…

  2. Why Chromosome Palindromes?

    Directory of Open Access Journals (Sweden)

    Esther Betrán

    2012-01-01

    Full Text Available We look at sex-limited chromosome (Y or W evolution with particular emphasis on the importance of palindromes. Y chromosome palindromes consist of inverted duplicates that allow for local recombination in an otherwise nonrecombining chromosome. Since palindromes enable intrachromosomal gene conversion that can help eliminate deleterious mutations, they are often highlighted as mechanisms to protect against Y degeneration. However, the adaptive significance of recombination resides in its ability to decouple the evolutionary fates of linked mutations, leading to both a decrease in degeneration rate and an increase in adaptation rate. Our paper emphasizes the latter, that palindromes may exist to accelerate adaptation by increasing the potential targets and fixation rates of incoming beneficial mutations. This hypothesis helps reconcile two enigmatic features of the “palindromes as protectors” view: (1 genes that are not located in palindromes have been retained under purifying selection for tens of millions of years, and (2 under models that only consider deleterious mutations, gene conversion benefits duplicate gene maintenance but not initial fixation. We conclude by looking at ways to test the hypothesis that palindromes enhance the rate of adaptive evolution of Y-linked genes and whether this effect can be extended to palindromes on other chromosomes.

  3. Ipl1/Aurora kinase suppresses S-CDK-driven spindle formation during prophase I to ensure chromosome integrity during meiosis.

    Directory of Open Access Journals (Sweden)

    Louise Newnham

    Full Text Available Cells coordinate spindle formation with DNA repair and morphological modifications to chromosomes prior to their segregation to prevent cell division with damaged chromosomes. Here we uncover a novel and unexpected role for Aurora kinase in preventing the formation of spindles by Clb5-CDK (S-CDK during meiotic prophase I and when the DDR is active in budding yeast. This is critical since S-CDK is essential for replication during premeiotic S-phase as well as double-strand break induction that facilitates meiotic recombination and, ultimately, chromosome segregation. Furthermore, we find that depletion of Cdc5 polo kinase activity delays spindle formation in DDR-arrested cells and that ectopic expression of Cdc5 in prophase I enhances spindle formation, when Ipl1 is depleted. Our findings establish a new paradigm for Aurora kinase function in both negative and positive regulation of spindle dynamics.

  4. Partial Hepatectomy in Acetylation-Deficient Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Yoo-Kyung Lee

    2014-12-01

    Full Text Available BackgroundAneuploidy has been suggested as one of the major causes of cancer from the time of Boveri. In support of this notion, many studies have shown that cancer cells exhibit aneuploidy. However, there are evidences that do not support the aneuploidy hypothesis. We have previously reported that the spindle assembly checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment. Mice heterozygous for acetylation-deficient BubR1 (K243R/+ spontaneously develop cancer with chromosome instability. As K243R/+ mice develop hepatocellular carcinoma, we set out to test if chromosome mis-segregation was the cause of their liver cancer.MethodsPrimary hepatocytes in the regenerating liver after partial hepatectomy (PH were analyzed and compared for various mitotic parameters.ResultsPrimary hepatocytes isolated from K243R/+ mice after PH displayed a marked increase of chromosome misalignment, accompanied by an increase of micronuclei. In comparison, the number of nuclei per cell and the centrosome numbers were not different between wild-type and K243R/+ mice. Taken together, chromosome mis-segregation provokes tumorigenesis in mouse liver.ConclusionOur results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.

  5. VHL loss causes spindle misorientation and chromosome instability.

    Science.gov (United States)

    Thoma, Claudio R; Toso, Alberto; Gutbrodt, Katrin L; Reggi, Sabina P; Frew, Ian J; Schraml, Peter; Hergovich, Alexander; Moch, Holger; Meraldi, Patrick; Krek, Wilhelm

    2009-08-01

    Error-free mitosis depends on fidelity-monitoring checkpoint systems that ensure correct temporal and spatial coordination of chromosome segregation by the microtubule spindle apparatus. Defects in these checkpoint systems can lead to genomic instability, an important aspect of tumorigenesis. Here we show that the von Hippel-Lindau (VHL) tumour suppressor protein, pVHL, which is inactivated in hereditary and sporadic forms of renal cell carcinoma, localizes to the mitotic spindle in mammalian cells and its functional inactivation provokes spindle misorientation, spindle checkpoint weakening and chromosomal instability. Spindle misorientation is linked to unstable astral microtubules and is supressed by the restoration of wild-type pVHL in pVHL-deficient cells, but not in naturally-occurring VHL disease mutants that are defective in microtubule stabilization. Impaired spindle checkpoint function and chromosomal instability are the result of reduced Mad2 (mitotic arrest deficient 2) levels actuated by pVHL-inactivation and are rescued by re-expression of either Mad2 or pVHL in VHL-defective cells. An association between VHL inactivation, reduced Mad2 levels and increased aneuploidy was also found in human renal cancer, implying that the newly identified functions of pVHL in promoting proper spindle orientation and chromosomal stability probably contribute to tumour suppression.

  6. Telomere dysfunction and chromosome instability

    Energy Technology Data Exchange (ETDEWEB)

    Murnane, John P., E-mail: jmurnane@radonc.ucsf.edu [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)

    2012-02-01

    The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is

  7. SOCIAL POLARIZATION AND SEGREGATION IN BEIJING

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The biggest change in Beijing during the last decade has been in its social structure. This transition is changing the existing situation of social "equality", and leads to polarization both in individual communities and in society as a whole. As a result, social variations and conflicting interest are growing, and some new social groups are emerging. In this paper we seek to explore a new urban phenomenon in post-1984 Beijing: social polarization and segregation. At first, we will discuss some elements explaining social polarization. The elements and the processes can be traced back to two main aspects of the economic reforms, namely the internal reforms unleashing a huge rural exodus and the open door policy. Special attention will be paid to the new lower end of the social ladder, which is made up largely by rural migrantsthat make up the so-called floating population.Finally we will explore how these social changes translate into urban segregation, with some consideration for future develop-ments.

  8. Highly Nonlinear Ising Model and Social Segregation

    CERN Document Server

    Sumour, M A; Shabat, M M

    2011-01-01

    The usual interaction energy of the random field Ising model in statistical physics is modified by complementing the random field by added to the energy of the usual Ising model a nonlinear term S^n were S is the sum of the neighbor spins, and n=0,1,3,5,7,9,11. Within the Schelling model of urban segregation, this modification corresponds to housing prices depending on the immediate neighborhood. Simulations at different temperatures, lattice size, magnetic field, number of neighbors and different time intervals showed that results for all n are similar, expect for n=3 in violation of the universality principle and the law of corresponding states. In order to find the critical temperatures, for large n we no longer start with all spins parallel but instead with a random configuration, in order to facilitate spin flips. However, in all cases we have a Curie temperature with phase separation or long-range segregation only below this Curie temperature, and it is approximated by a simple formula: Tc is proportion...

  9. Theta oscillations accompanying concurrent auditory stream segregation.

    Science.gov (United States)

    Tóth, Brigitta; Kocsis, Zsuzsanna; Urbán, Gábor; Winkler, István

    2016-08-01

    The ability to isolate a single sound source among concurrent sources is crucial for veridical auditory perception. The present study investigated the event-related oscillations evoked by complex tones, which could be perceived as a single sound and tonal complexes with cues promoting the perception of two concurrent sounds by inharmonicity, onset asynchrony, and/or perceived source location difference of the components tones. In separate task conditions, participants performed a visual change detection task (visual control), watched a silent movie (passive listening) or reported for each tone whether they perceived one or two concurrent sounds (active listening). In two time windows, the amplitude of theta oscillation was modulated by the presence vs. absence of the cues: 60-350ms/6-8Hz (early) and 350-450ms/4-8Hz (late). The early response appeared both in the passive and the active listening conditions; it did not closely match the task performance; and it had a fronto-central scalp distribution. The late response was only elicited in the active listening condition; it closely matched the task performance; and it had a centro-parietal scalp distribution. The neural processes reflected by these responses are probably involved in the processing of concurrent sound segregation cues, in sound categorization, and response preparation and monitoring. The current results are compatible with the notion that theta oscillations mediate some of the processes involved in concurrent sound segregation.

  10. [Dicentric Y chromosome].

    Science.gov (United States)

    Abdelmoula, N Bouayed; Amouri, A

    2005-01-01

    Dicentric Y chromosomes are the most common Y structural abnormalities and their influence on gonadal and somatic development is extremely variable. Here, we report the third comprehensive review of the literature concerning dicentric Y chromosomes reported since 1994. We find 78 new cases for which molecular studies (PCR or FISH) have been widely applied to investigate SRY (68% of cases), GBY, ZFY, RFS4Y, GCY and different genes at AZF region. For dic(Yq), all cases (n = 20) were mosaic for 45,X and 4 of them were also mosaic for a 46,XY cell line. When breakpoints were available (15/20 cases), they were in Yp11. 50% of cases were phenotypic female and 20% phenotypic male while 20% of cases were reported with gonadal dysgenesis. Gonadal histology was defined in 8 cases but only in one case, gonadal tissu was genetically investigated because of gonadoblastoma. For dic(Yp) (n = 55), mosaicism concerned only 45,X cell line and was found in 50 cases while the remainder five cases were homogeneous. When breakpoints were available, it was at Yq11 in 50 cases and at Yq12 in two cases. 54% of cases were phenotypic female, 26% were phenotypic male and 18% were associated with genitalia ambiguous. SRY was analyzed in 33 cases, sequenced in 9 cases and was muted in only one case. Gonads were histologically explored in 34 cases and genetically investigated in 8 cases. Gonadoblastoma was found in only two cases. Through this review, it seems that phenotype-genotype correlations are still not possible and that homogeneous studies of dic(Y) in more patients using molecular tools for structural characterization of the rearranged Y chromosome and assessment of mosaicism in many organs are necessary to clarify the basis of the phenotypic heterogeneity of dicentric Y chromosomes and then to help phenotypic prediction of such chromosome rearrangement.

  11. Binomial mitotic segregation of MYCN-carrying double minutes in neuroblastoma illustrates the role of randomness in oncogene amplification.

    Directory of Open Access Journals (Sweden)

    Gisela Lundberg

    Full Text Available BACKGROUND: Amplification of the oncogene MYCN in double minutes (DMs is a common finding in neuroblastoma (NB. Because DMs lack centromeric sequences it has been unclear how NB cells retain and amplify extrachromosomal MYCN copies during tumour development. PRINCIPAL FINDINGS: We show that MYCN-carrying DMs in NB cells translocate from the nuclear interior to the periphery of the condensing chromatin at transition from interphase to prophase and are preferentially located adjacent to the telomere repeat sequences of the chromosomes throughout cell division. However, DM segregation was not affected by disruption of the telosome nucleoprotein complex and DMs readily migrated from human to murine chromatin in human/mouse cell hybrids, indicating that they do not bind to specific positional elements in human chromosomes. Scoring DM copy-numbers in ana/telophase cells revealed that DM segregation could be closely approximated by a binomial random distribution. Colony-forming assay demonstrated a strong growth-advantage for NB cells with high DM (MYCN copy-numbers, compared to NB cells with lower copy-numbers. In fact, the overall distribution of DMs in growing NB cell populations could be readily reproduced by a mathematical model assuming binomial segregation at cell division combined with a proliferative advantage for cells with high DM copy-numbers. CONCLUSION: Binomial segregation at cell division explains the high degree of MYCN copy-number variability in NB. Our findings also provide a proof-of-principle for oncogene amplification through creation of genetic diversity by random events followed by Darwinian selection.

  12. Novel ATRX gene damaging missense mutation c.6740A>C segregates with profound to severe intellectual deficiency without alpha thalassaemia

    Directory of Open Access Journals (Sweden)

    Habib Bouazzi

    2016-01-01

    Interpretation & conclusions: The novel mutation c.6740A>C was identified within the ATRX gene helicase domain and confirmed by Sanger sequencing in the three affected males as well as in the mother and her two daughters. This mutation was predicted to be damaging and deleterious. The novel mutation segregated with the phenotype without alpha-thalassaemia and with non-skewed X chromosome.

  13. Linear Chromosome-generating System of Agrobacterium tumefaciens C58

    Science.gov (United States)

    Huang, Wai Mun; DaGloria, Jeanne; Fox, Heather; Ruan, Qiurong; Tillou, John; Shi, Ke; Aihara, Hideki; Aron, John; Casjens, Sherwood

    2012-01-01

    Agrobacterium tumefaciens C58, the pathogenic bacteria that causes crown gall disease in plants, harbors one circular and one linear chromosome and two circular plasmids. The telomeres of its unusual linear chromosome are covalently closed hairpins. The circular and linear chromosomes co-segregate and are stably maintained in the organism. We have determined the sequence of the two ends of the linear chromosome thus completing the previously published genome sequence of A. tumefaciens C58. We found that the telomeres carry nearly identical 25-bp sequences at the hairpin ends that are related by dyad symmetry. We further showed that its Atu2523 gene encodes a protelomerase (resolvase) and that the purified enzyme can generate the linear chromosomal closed hairpin ends in a sequence-specific manner. Agrobacterium protelomerase, whose presence is apparently limited to biovar 1 strains, acts via a cleavage-and-religation mechanism by making a pair of transient staggered nicks invariably at 6-bp spacing as the reaction intermediate. The enzyme can be significantly shortened at both the N and C termini and still maintain its enzymatic activity. Although the full-length enzyme can uniquely bind to its product telomeres, the N-terminal truncations cannot. The target site can also be shortened from the native 50-bp inverted repeat to 26 bp; thus, the Agrobacterium hairpin-generating system represents the most compact activity of all hairpin linear chromosome- and plasmid-generating systems to date. The biochemical analyses of the protelomerase reactions further revealed that the tip of the hairpin telomere may be unusually polymorphically capable of accommodating any nucleotide. PMID:22582388

  14. Modelling density segregation in flowing bidisperse granular materials

    Science.gov (United States)

    Xiao, Hongyi; Umbanhowar, Paul B.; Ottino, Julio M.; Lueptow, Richard M.

    2016-07-01

    Preventing segregation in flowing granular mixtures is an ongoing challenge for industrial processes that involve the handling of bulk solids. A recent continuum-based modelling approach accurately predicts spatial concentration fields in a variety of flow geometries for mixtures varying in particle size. This approach captures the interplay between advection, diffusion and segregation using kinematic information obtained from experiments and/or discrete element method (DEM) simulations combined with an empirically determined relation for the segregation velocity. Here, we extend the model to include density-driven segregation, thereby validating the approach for the two important cases of practical interest. DEM simulations of density bidisperse flows of mono-sized particles in a quasi-two-dimensional-bounded heap were performed to determine the dependence of the density-driven segregation velocity on local shear rate and particle concentration. The model yields theoretical predictions of segregation patterns that quantitatively match the DEM simulations over a range of density ratios and flow rates. Matching experiments reproduce the segregation patterns and quantitative segregation profiles obtained in both the simulations and the model, thereby demonstrating that the modelling approach captures the essential physics of density-driven segregation in granular heap flow.

  15. Requirements for the evaluation of computational speech segregation systems.

    Science.gov (United States)

    May, Tobias; Dau, Torsten

    2014-12-01

    Recent studies on computational speech segregation reported improved speech intelligibility in noise when estimating and applying an ideal binary mask with supervised learning algorithms. However, an important requirement for such systems in technical applications is their robustness to acoustic conditions not considered during training. This study demonstrates that the spectro-temporal noise variations that occur during training and testing determine the achievable segregation performance. In particular, such variations strongly affect the identification of acoustical features in the system associated with perceptual attributes in speech segregation. The results could help establish a framework for a systematic evaluation of future segregation systems.

  16. Requirements for the evaluation of computational speech segregation systems

    DEFF Research Database (Denmark)

    May, Tobias; Dau, Torsten

    2014-01-01

    Recent studies on computational speech segregation reported improved speech intelligibility in noise when estimating and applying an ideal binary mask with supervised learning algorithms. However, an important requirement for such systems in technical applications is their robustness to acoustic...... conditions not considered during training. This study demonstrates that the spectro-temporal noise variations that occur during training and testing determine the achievable segregation performance. In particular, such variations strongly affect the identification of acoustical features in the system...... associated with perceptual attributes in speech segregation. The results could help establish a framework for a systematic evaluation of future segregation systems....

  17. Dynamics of X Chromosome Inactivation

    NARCIS (Netherlands)

    F. Loos (Friedemann)

    2015-01-01

    markdownabstract__Abstract__ Dosage compensation evolved to account for the difference in expression of sex chromosome-linked genes. In mammals dosage compensation is achieved by inactivation of one X chromosome during early female embryogenesis in a process called X chromosome inactivation (XCI).

  18. Chromosomal breakpoints characterization of two supernumerary ring chromosomes 20.

    Science.gov (United States)

    Guediche, N; Brisset, S; Benichou, J-J; Guérin, N; Mabboux, P; Maurin, M-L; Bas, C; Laroudie, M; Picone, O; Goldszmidt, D; Prévot, S; Labrune, P; Tachdjian, G

    2010-02-01

    The occurrence of an additional ring chromosome 20 is a rare chromosome abnormality, and no common phenotype has been yet described. We report on two new patients presenting with a supernumerary ring chromosome 20 both prenatally diagnosed. The first presented with intrauterine growth retardation and some craniofacial dysmorphism, and the second case had a normal phenotype except for obesity. Conventional cytogenetic studies showed for each patient a small supernumerary marker chromosome (SMC). Using fluorescence in situ hybridization, these SMCs corresponded to ring chromosomes 20 including a part of short and long arms of chromosome 20. Detailed molecular cytogenetic characterization showed different breakpoints (20p11.23 and 20q11.23 for Patient 1 and 20p11.21 and 20q11.21 for Patient 2) and sizes of the two ring chromosomes 20 (13.6 Mb for case 1 and 4.8 Mb for case 2). Review of the 13 case reports of an extra r(20) ascertained postnatally (8 cases) and prenatally (5 cases) showed varying degrees of phenotypic abnormalities. We document a detailed molecular cytogenetic chromosomal breakpoints characterization of two cases of supernumerary ring chromosomes 20. These results emphasize the need to characterize precisely chromosomal breakpoints of supernumerary ring chromosomes 20 in order to establish genotype-phenotype correlation. This report may be helpful for prediction of natural history and outcome, particularly in prenatal diagnosis.

  19. Familial complex chromosomal rearrangement resulting in a recombinant chromosome.

    Science.gov (United States)

    Berend, Sue Ann; Bodamer, Olaf A F; Shapira, Stuart K; Shaffer, Lisa G; Bacino, Carlos A

    2002-05-15

    Familial complex chromosomal rearrangements (CCRs) are rare and tend to involve fewer breakpoints and fewer chromosomes than CCRs that are de novo in origin. We report on a CCR identified in a child with congenital heart disease and dysmorphic features. Initially, the child's karyotype was thought to involve a straightforward three-way translocation between chromosomes 3, 8, and 16. However, after analyzing the mother's chromosomes, the mother was found to have a more complex rearrangement that resulted in a recombinant chromosome in the child. The mother's karyotype included an inverted chromosome 2 and multiple translocations involving chromosomes 3, 5, 8, and 16. No evidence of deletion or duplication that could account for the clinical findings in the child was identified.

  20. Micro and Macro Segregation in Alloys Solidifying with Equiaxed Morphology

    Science.gov (United States)

    Stefanescu, Doru M.; Curreri, Peter A.; Leon-Torres, Jose; Sen, Subhayu

    1996-01-01

    To understand macro segregation formation in Al-Cu alloys, experiments were run under terrestrial gravity (1g) and under low gravity during parabolic flights (10(exp -2) g). Alloys of two different compositions (2% and 5% Cu) were solidified at two different cooling rates. Systematic microscopic and SEM observations produced microstructural and segregation maps for all samples. These maps may be used as benchmark experiments for validation of microstructure evolution and segregation models. As expected, the macro segregation maps are very complex. When segregation was measured along the central axis of the sample, the highest macro segregation for samples solidified at 1g was obtained for the lowest cooling rate. This behavior is attributed to the longer time available for natural convection and shrinkage flow to affect solute redistribution. In samples solidified under low-g, the highest macro-segregation was obtained at the highest cooling rate. In general, low-gravity solidification resulted in less segregation. To explain the experimental findings, an analytical (Flemings-Nereo) and a numerical model were used. For the numerical model, the continuum formulation was employed to describe the macroscopic transports of mass, energy, and momentum, associated with the microscopic transport phenomena, for a two-phase system. The model proposed considers that liquid flow is driven by thermal and solutal buoyancy, and by solidification shrinkage. The Flemings-Nereo model explains well macro segregation in the initial stages of low-gravity segregation. The numerical model can describe the complex macro segregation pattern and the differences between low- and high-gravity solidification.

  1. Aurora B prevents chromosome arm separation defects by promoting telomere dispersion and disjunction.

    Science.gov (United States)

    Reyes, Céline; Serrurier, Céline; Gauthier, Tiphaine; Gachet, Yannick; Tournier, Sylvie

    2015-03-16

    The segregation of centromeres and telomeres at mitosis is coordinated at multiple levels to prevent the formation of aneuploid cells, a phenotype frequently observed in cancer. Mitotic instability arises from chromosome segregation defects, giving rise to chromatin bridges at anaphase. Most of these defects are corrected before anaphase onset by a mechanism involving Aurora B kinase, a key regulator of mitosis in a wide range of organisms. Here, we describe a new role for Aurora B in telomere dispersion and disjunction during fission yeast mitosis. Telomere dispersion initiates in metaphase, whereas disjunction takes place in anaphase. Dispersion is promoted by the dissociation of Swi6/HP1 and cohesin Rad21 from telomeres, whereas disjunction occurs at anaphase after the phosphorylation of condensin subunit Cnd2. Strikingly, we demonstrate that deletion of Ccq1, a telomeric shelterin component, rescued cell death after Aurora inhibition by promoting the loading of condensin on chromosome arms. Our findings reveal an essential role for telomeres in chromosome arm segregation.

  2. Asymmetry of Chromosome Replichores Renders the DNA Translocase Activity of FtsK Essential for Cell Division and Cell Shape Maintenance in Escherichia coli

    OpenAIRE

    Christian Lesterlin; Carine Pages; Nelly Dubarry; Santanu Dasgupta; François Cornet

    2008-01-01

    Bacterial chromosomes are organised as two replichores of opposite polarity that coincide with the replication arms from the ori to the ter region. Here, we investigated the effects of asymmetry in replichore organisation in Escherichia coli. We show that large chromosome inversions from the terminal junction of the replichores disturb the ongoing post-replicative events, resulting in inhibition of both cell division and cell elongation. This is accompanied by alterations of the segregation p...

  3. Chromosome 19 International Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Pericak-Vance, M.A. (Duke Univ., Durham, NC (United States). Medical Center); Ropers, H.H. (Univ. Hospital Nijmegen, (The Netherlands). Dept. of Human Genetics); Carrano, A.J. (Lawrence Livermore National Lab., CA (United States))

    1993-01-04

    The Second International Workshop on Human Chromosome 19 was hosted on January 25 and 26, 1992, by the Department of Human Genetics, University Hospital Nijmegen, The Netherlands, at the 'Meerdal Conference Center'. The workshop was supported by a grant from the European Community obtained through HUGO, the Dutch Research Organization (NWO) and the Muscular Dystrophy Association (MDA). Travel support for American participants was provided by the Department of Energy. The goals of this workshop were to produce genetic, physical and integrated maps of chromosome 19, to identify inconsistencies and gaps, and to discuss and exchange resources and techniques available for the completion of these maps. The second day of the meeting was largely devoted to region or disease specific efforts. In particular, the meeting served as a platform for assessing and discussing the recent progress made into the molecular elucidation of myotonic dystrophy.

  4. A computer model of auditory stream segregation.

    Science.gov (United States)

    Beauvois, M W; Meddis, R

    1991-08-01

    A computer model is described which simulates some aspects of auditory stream segregation. The model emphasizes the explanatory power of simple physiological principles operating at a peripheral rather than a central level. The model consists of a multi-channel bandpass-filter bank with a "noisy" output and an attentional mechanism that responds selectively to the channel with the greatest activity. A "leaky integration" principle allows channel excitation to accumulate and dissipate over time. The model produces similar results to two experimental demonstrations of streaming phenomena, which are presented in detail. These results are discussed in terms of the "emergent properties" of a system governed by simple physiological principles. As such the model is contrasted with higher-level Gestalt explanations of the same phenomena while accepting that they may constitute complementary kinds of explanation.

  5. Segregation and differential settling in flocculated tailings

    Energy Technology Data Exchange (ETDEWEB)

    Farinato, R.S.; Mahmoudkhani, A.; Fenderson, T.; Watson, P. [Kemira, Atlanta, GA (United States)

    2010-07-01

    Untreated oil sands tailings have a high solids content, have poor dewaterability, and contain no aggregates. This PowerPoint presentation investigated segregation and differential settling in flocculated tailings. Tailings were treated with gypsum and various polymers. Cylinder settling, dynamic rheometry, particle size analysis, and microscopy techniques were used to characterize the composite tailings. The particles sizes of the samples were evaluated in relation to shear rate, bed depth, and treatment. The study showed that the gypsum-treated tailings had small aggregates, size stratification, a high solids content, and poor dewaterability. The polymer N-treated tailings had the lowest solids content, good dewaterability, and weak aggregates. The polymer A-treated tailings had a low solids content, very good dewaterability, and strong aggregates. The addition of a coagulant to the polymer-A treated tailings provided weaker aggregates and a higher solids content. tabs., figs.

  6. Segregation induced fingering instabilities in granular avalanches

    Science.gov (United States)

    Woodhouse, Mark; Thornton, Anthony; Johnson, Chris; Kokelaar, Pete; Gray, Nico

    2013-04-01

    It is important to be able to predict the distance to which a hazardous natural granular flows (e.g. snow slab avalanches, debris-flows and pyroclastic flows) might travel, as this information is vital for accurate assessment of the risks posed by such events. In the high solids fraction regions of these flows the large particles commonly segregate to the surface, where they are transported to the margins to form bouldery flow fronts. In many natural flows these bouldery margins experience a much greater frictional force, leading to frontal instabilities. These instabilities create levees that channelize the flow vastly increasing the run-out distance. A similar effect can be observed in dry granular experiments, which use a combination of small round and large rough particles. When this mixture is poured down an inclined plane, particle size segregation causes the large particles to accumulate near the margins. Being rougher, the large particles experience a greater friction force and this configuration (rougher material in front of smoother) can be unstable. The instability causes the uniform flow front to break up into a series of fingers. A recent model for particle size-segregation has been coupled to existing avalanche models through a particle concentration dependent friction law. In this talk numerical solutions of this coupled system are presented and compared to both large scale experiments carried out at the USGS flume and more controlled small scale laboratory experiments. The coupled depth-averaged model captures the accumulation of large particles at the flow front. We show this large particle accumulation at the head of the flow can lead to the break-up of the initially uniform front into a series of fingers. However, we are unable to obtain a fully grid-resolved numerical solution; the width of the fingers decreases as the grid is refined. By considering the linear stability of a steady, fully-developed, bidisperse granular layer it is shown that

  7. Heider balance, asymmetric ties, and gender segregation

    Science.gov (United States)

    Krawczyk, Małgorzata J.; del Castillo-Mussot, Marcelo; Hernández-Ramírez, Eric; Naumis, Gerardo G.; Kułakowski, Krzysztof

    2015-12-01

    To remove a cognitive dissonance in interpersonal relations, people tend to divide their acquaintances into friendly and hostile parts, both groups internally friendly and mutually hostile. This process is modeled as an evolution toward the Heider balance. A set of differential equations have been proposed and validated (Kułakowski et al., 2005) to model the Heider dynamics of this social and psychological process. Here we generalize the model by including the initial asymmetry of the interpersonal relations and the direct reciprocity effect which removes this asymmetry. Our model is applied to the data on enmity and friendship in 37 school classes and 4 groups of teachers in México. For each class, a stable balanced partition is obtained into two groups. The gender structure of the groups reveals stronger gender segregation in younger classes, i.e. of age below 12 years, a fact consistent with other general empirical results.

  8. Heider balance, asymmetric ties, and gender segregation

    CERN Document Server

    Krawczyk, Małgorzata J; Hernández-Ramirez, Eric; Naumis, Gerardo G; Kułakowski, Krzysztof

    2015-01-01

    To remove a cognitive dissonance in interpersonal relations, people tend to divide our acquaintances into friendly and hostile parts, both groups internally friendly and mutually hostile. This process is modeled as an evolution towards the Heider balance. A set of differential equations have been proposed and validated (Kulakowski {\\it et al}, IJMPC 16 (2005) 707) to model the Heider dynamics of this social and psychological process. Here we generalize the model by including the initial asymmetry of the interprersonal relations and the direct reciprocity effect which removes this asymmetry. Our model is applied to the data on enmity and friendship in 37 school classes and 4 groups of teachers in M\\'exico. For each class, a stable balanced partition is obtained into two groups. The gender structure of the groups reveals stronger gender segregation in younger classes, i.e. of age below 12 years, a fact consistent with other general empirical results.

  9. Ethnic Segregation in Arizona Charter Schools

    Directory of Open Access Journals (Sweden)

    Casey D. Cobb

    1999-01-01

    Full Text Available Among the criticisms of charter schools is their potential to further stratify schools along ethnic and class lines. This study addressed whether Arizona charter schools are more ethnically segregated than traditional public schools. In 1996-97, Arizona had nearly one in four of all charter schools in the United States. The analysis involved a series of comparisons between the ethnic compositions of adjacent charter and public schools in Arizona's most populated region and its rural towns. This methodology differed from the approach of many evaluations of charter schools and ethnic stratification in that it incorporated the use of geographic maps to compare schools' ethnic make-ups. The ethnic compositions of 55 urban and 57 rural charter schools were inspected relative to their traditional public school neighbors.

  10. A stable acentric marker chromosome: Possible existence of an intercalary ancient centromere at distal 8p

    Energy Technology Data Exchange (ETDEWEB)

    Ohashi, Hirofumi; Fukushima, Yoshimitsu; Wakui, Keiko; Ogawa, Kioyshi [Saitama Children`s Medical Center, Iwatsuki (Japan); Okano, Tetsuroh [Kitazato Univ., Tokyo (Japan); Niikawa, Norio [Nagasaki Univ. School of Medicine (Japan)

    1994-12-01

    A centromere is considered to be an essential chromosomal component where microtubule-kinetochore interaction occurs to segregate sister chromatids faithfully and acentric chromosomes are unstable and lost through cell divisions. We report a novel marker chromosome that was acentric but stable through cell divisions. The patient was a 2-year-old girl with mental retardation, patent ductus arteriosus, and mild dysmorphic features. G-banded chromosome analysis revealed that an additional small marker chromosome was observed in all 100 cells examined. By the reverse-chromosome-painting method, the marker was found to originate from the distal region of 8p, and a subsequent two-color FISH analysis with cosmid probes around the region revealed that the marker was an inverted duplication interpreted as 8pter {yields} p23.1::p23.1 {yields} 8pter. No centromeric region was involved in the marker. By FISH, no {alpha}-satellite sequence was detected on the marker, while a telomere sequence was detected at each end. Anti-kinetochore immunostaining, using a serum from a patient with CREST (calcinosis, Raynaud syndrome, esophageal dismotility, sclerodactyly, and telangiectasia) syndrome, showed a pair of signals on the marker, which indicated that a functional kinetochore was present on the marker. The analysis of this patient might suggest the possibility that an ancient centromere sequence exists at distal 8p (8p23.1-pter) and was activated through the chromosome rearrangement in the patient.

  11. The impact of imprinting: Prader-Willi syndrome resulting from chromosome translocation, recombination, and nondisjunction

    Energy Technology Data Exchange (ETDEWEB)

    Toth-Fejel, S.; Olson, S.; Gunter, K. [Oregon Health Sciences Univ., Portland, OR (United States)] [and others

    1996-05-01

    Prader-Willi syndrome (PWS) is most often the result of a deletion of bands q11.2-q13 of the paternally derived chromosome 15, but it also occurs either because of maternal uniparental disomy (UPD) of this region or, rarely, from a methylation imprinting defect. A significant number of cases are due to structural rearrangements of the pericentromeric region of chromosome 15. We report two cases of PWS with UPD in which there was a meiosis I nondisjunction error involving an altered chromosome 15 produced by both a translocation event between the heteromorphic satellite regions of chromosomes 14 and 15 and recombination. In both cases, high-resolution banding of the long arm was normal, and FISH of probes D15S11, SNRPN, D15S10, and GABRB3 indicated no loss of this material. Chromosome heteromorphism analysis showed that each patient had maternal heterodisomy of the chromosome 15 short arm, whereas PCR of microsatellites demonstrated allele-specific maternal isodisomy and heterodisomy of the long arm. SNRPN gene methylation analysis revealed only a maternal imprint in both patients. We suggest that the chromosome structural rearrangements, combined with recombination in these patients, disrupted normal segregation of an imprinted region, resulting in uniparental disomy and PWS. 30 refs., 6 figs., 1 tab.

  12. Cyclin G-associated kinase promotes microtubule outgrowth from chromosomes during spindle assembly.

    Science.gov (United States)

    Tanenbaum, Marvin E; Vallenius, Tea; Geers, Erica F; Greene, Lois; Mäkelä, Tomi P; Medema, Rene H

    2010-08-01

    During mitosis, all chromosomes must attach to microtubules of the mitotic spindle to ensure correct chromosome segregation. Microtubule attachment occurs at specialized structures at the centromeric region of chromosomes, called kinetochores. These kinetochores can generate microtubule attachments through capture of centrosome-derived microtubules, but in addition, they can generate microtubules themselves, which are subsequently integrated with centrosome-derived microtubules to form the mitotic spindle. Here, we have performed a large scale RNAi screen and identify cyclin G-associated kinase (GAK) as a novel regulator of microtubule generation at kinetochores/chromatin. This function of GAK requires its C-terminal J-domain, which is essential for clathrin recycling from endocytic vesicles. Consistently, cells lacking GAK show strongly reduced levels of clathrin on the mitotic spindle, and reduction of clathrin levels also inhibits microtubule generation at kinetochores/chromosomes. Finally, we present evidence that association of clathrin with the spindle is promoted by a signal coming from the chromosomes. These results identify a role for GAK and clathrin in microtubule outgrowth from kinetochores/chromosomes and suggest that GAK acts through clathrin to control microtubule outgrowth around chromosomes.

  13. Bombardment-induced segregation and redistribution

    Energy Technology Data Exchange (ETDEWEB)

    Lam, N.Q.; Wiedersich, H.

    1986-04-01

    During ion bombardment, a number of processes can alter the compositional distribution and microstructure in near-surface regions of alloys. The relative importance of each process depends principally on the target composition, temperature, and ion characteristics. In addition to displacement mixing leading to a randomization of atomic locations, and preferential loss of alloying elements by sputtering, which are dominant at relatively low temperatures, several thermally-activated processes, including radiation-enhanced diffusion, radiation-induced segregation and Gibbsian adsorption, also play important roles. At elevated temperatures, nonequilibrium point defects induced by ion impacts become mobile and tend to anneal out by recombination and diffusion to extended sinks, such as dislocations, grain boundaries and free surfaces. The high defect concentrations, far exceeding the thermodynamic equilbrium values, can enhance diffusion-controlled processes, while persistent defect fluxes, originating from the spatial non-uniformity in defect production and annihilation, give rise to local redistribution of alloy constituents because of radiation-induced segregation. Moreover, when the alloy is maintained at high temperature, Gibbsian adsorption, driven by the reduction in free energy of the system, occurs even without irradiation; it involves a compositional perturbation in a few atom layers near the alloy surface. The combination of these processes leads to the complex development of a compositionally-modified layer in the subsurface region. In the present paper, selected examples of these different phenomena and their synergistic effects on the evolution of the near-surface compositions of alloys during sputtering and ion implantation at elevated temperatures are discussed. 74 refs., 7 figs., 1 tab.

  14. Protein diversity confers specificity in plasmid segregation.

    Science.gov (United States)

    Fothergill, Timothy J G; Barillà, Daniela; Hayes, Finbarr

    2005-04-01

    The ParG segregation protein (8.6 kDa) of multidrug resistance plasmid TP228 is a homodimeric DNA-binding factor. The ParG dimer consists of intertwined C-terminal domains that adopt a ribbon-helix-helix architecture and a pair of flexible, unstructured N-terminal tails. A variety of plasmids possess partition loci with similar organizations to that of TP228, but instead of ParG homologs, these plasmids specify a diversity of unrelated, but similarly sized, partition proteins. These include the proteobacterial pTAR, pVT745, and pB171 plasmids. The ParG analogs of these plasmids were characterized in parallel with the ParG homolog encoded by the pseudomonal plasmid pVS1. Like ParG, the four proteins are dimeric. No heterodimerization was detectable in vivo among the proteins nor with the prototypical ParG protein, suggesting that monomer-monomer interactions are specific among the five proteins. Nevertheless, as with ParG, the ParG analogs all possess significant amounts of unordered amino acid residues, potentially highlighting a common structural link among the proteins. Furthermore, the ParG analogs bind specifically to the DNA regions located upstream of their homologous parF-like genes. These nucleoprotein interactions are largely restricted to cognate protein-DNA pairs. The results reveal that the partition complexes of these and related plasmids have recruited disparate DNA-binding factors that provide a layer of specificity to the macromolecular interactions that mediate plasmid segregation.

  15. A balanced translocation disrupting BCL2L10 and PNLDC1 segregates with affective psychosis

    Science.gov (United States)

    Bouwkamp, Christian G.; Kievit, Anneke J. A.; Olgiati, Simone; Breedveld, Guido J.; Coesmans, Michiel; Bonifati, Vincenzo

    2016-01-01

    Affective psychoses are a group of severe psychiatric disorders, including schizoaffective disorder and bipolar I disorder, together affecting ∼1% of the population. Despite their high heritability, the molecular genetics and neurobiology of affective psychosis remain largely elusive. Here, we describe the identification of a structural genetic variant segregating with affective psychosis in a family with multiple members suffering from bipolar I disorder or schizoaffective disorder, bipolar type. A balanced translocation involving chromosomes 6 and 15 was detected by karyotyping and fluorescence in‐situ hybridization (FISH). Using whole‐genome sequencing, we rapidly delineated the translocation breakpoints as corresponding intragenic events disrupting BCL2L10 and PNLDC1. These data warrant further consideration for BCL2L10 and PNLDC1 as novel candidates for affective psychosis. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc. PMID:27260655

  16. 41 CFR 60-1.8 - Segregated facilities.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Segregated facilities. 60...; Compliance Reports § 60-1.8 Segregated facilities. To comply with its obligations under the Order, a contractor must ensure that facilities provided for employees are provided in such a manner that...

  17. Effects of Network Segregation in Intergroup Conflict : An Experimental Analysis

    NARCIS (Netherlands)

    Takács, Károly

    2006-01-01

    Dense in-group and scarce out-group relations (network segregation) often support the emergence of conflicts between groups. A key underlying mechanism is social control that helps to overcome the collective action problem within groups, but contributes to harmful conflicts among them in segregated

  18. Coleman Revisited: School Segregation, Peers, and Frog Ponds

    Science.gov (United States)

    Goldsmith, Pat Rubio

    2011-01-01

    Students from minority segregated schools tend to achieve and attain less than similar students from White segregated schools. This study examines whether peer effects can explain this relationship using normative models and frog-pond models. Normative models (where peers become alike) suggest that minority schoolmates are a liability. Frog-pond…

  19. 46 CFR 111.60-9 - Segregation of vital circuits.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Segregation of vital circuits. 111.60-9 Section 111.60-9...-GENERAL REQUIREMENTS Wiring Materials and Methods § 111.60-9 Segregation of vital circuits. (a) General. A branch circuit that supplies equipment vital to the propulsion, control, or safety of the vessel must...

  20. Educational Justice and Socio-Economic Segregation in Schools

    Science.gov (United States)

    Brighouse, Harry

    2007-01-01

    Sociologists exploring educational injustice often focus on socio-economic segregation as a central measure of injustice. The comprehensive ideal, furthermore, has the idea of socio-economic integration built into it. The current paper argues that socio-economic segregation is valuable only insofar as it serves other, more fundamental values. This…

  1. Sulfur segregation in titanium and selected titanium alloys

    Science.gov (United States)

    Outlaw, R. A.; Lee, W. S.; Hoekje, S. J.; Sankaran, S. N.

    1994-10-01

    The segregation of S in electrotransport-purified polycrystalline α-Ti and in several polycrystalline Ti alloys has been studied by Auger electron spectroscopy and ion scattering spectroscopy in the temperature range extending from 20 to 1000°C. The chemisorbed oxygen and carbon on Ti were observed to disappear at T ≈ 400°C after which the S signal increased to levels approaching 0.5 monolayer. At lower temperatures the presence of the surface oxygen and carbon appeared to inhibit the segregation, presumably because there were no available surfaces sites for the S emerging from the bulk. The activation energy for the S segregation in pure polycrystalline Ti was determined to be 16.7 kcal/mol, which, when compared to S segregation from single-crystal Ti, is quite small and suggest grain boundary or defect diffusion segregation kinetics. In the Ti-aluminide alloys, the presence of Al appeared to enhance the retention of surface oxygen which, in turn, substantially reduced the S segregation. The γ alloy, with its high Al content, exhibited the greatest retention of surface oxygen and the smallest quantity of S segregation ( T ≈ 1000°C). On the other hand, the β-21S alloy exhibited a greater segregation rate for the S than did α-Ti.

  2. "Brown" at 62: School Segregation by Race, Poverty and State

    Science.gov (United States)

    Orfield, Gary; Ee, Jongyeon; Frankenberg, Erica; Siegel-Hawley, Genevieve

    2016-01-01

    As the anniversary of "Brown v. Board of Education" decision arrives again without any major initiatives to mitigate spreading and deepening segregation in the nation's schools, the Civil Rights Project adds to a growing national discussion with a research brief drawn from a much broader study of school segregation to be published in…

  3. Standardized Testing and School Segregation: Like Tinder for Fire?

    Science.gov (United States)

    Knoester, Matthew; Au, Wayne

    2017-01-01

    Recent research suggests that high-stakes standardized testing has played a negative role in the segregation of children by race and class in schools. In this article we review research on the overall effects of segregation, the positive and negative aspects of how desegregation plans were carried out following the 1954 Supreme Court decision…

  4. Figure-ground segregation in a recurrent network architecture

    NARCIS (Netherlands)

    Lamme, V.A.F.; Roelfsema, P.R.; Spekreijse, H.; Bosch, H.

    2002-01-01

    Proposes a model of how the visual brain segregate textured scenes into figures and background. During texture segregation, locations where the properties of texture elements change abruptly are assigned to boundaries, whereas image regions that are relatively homogeneous are grouped together bounda

  5. Compositional Segregation in Unidirectionally Solidified Solid Solution Crystals

    Science.gov (United States)

    Wang, J. C.

    1983-01-01

    A computer program was developed to model compositional segregation in unidrectionally solidified solid-solution-semiconducting crystals. The program takes into account the variations of the interface segregation constant and solidification rate with composition. Calculations are performed for the HgCdTe solid solution system that is compared with experimental data.

  6. Sexual segregation in vertebrates: proximate and ultimate causes.

    Science.gov (United States)

    Ruckstuhl, K E

    2007-08-01

    Sexual segregation is very common in vertebrates that live in groups. In this article, I will review proximate and ultimate causes of sexual segregation in social species and in particular in ungulates in which the bulk of research on the topic has been carried out. In most social ungulate species, males and females live in separate groups outside the breeding season, sometimes using different home ranges and types of habitat. In most of these species, males are larger than females. Dimorphism in body size can lead to sexual differences in ecology and behavior making it difficult for the two sexes to stay in the same group. It is important for our better understanding of the evolution of sociality, sexual dimorphism and different mating systems to determine why sexual segregation is so widespread not only in ungulates but also in other vertebrates. In this article, I discuss the ecology of the two sexes by reviewing proximate and ultimate causes of sexual segregation. To do this, I compare a range of studies of ruminants and include explanations for social segregation as well as for habitat segregation by gender. This leads into a review and updates current knowledge of the phenomenon. Although I present a number of different hypotheses, I focus in particular on predation risk, forage selection and activity budget and discuss the social-factors hypothesis. I stress that the key in solving the enigma of sexual segregation lies in clearly separating hypotheses that try to explain social segregation and habitat segregation, as well as in including experiments or model systems. To that end, I present a preliminary study on a test of the activity-budget hypothesis in three-spine sticklebacks and explain why I believe that shoaling fish are useful for analysing the underlying processes and mechanisms that lead to sexual segregation in animals. Lastly, I argue that it is unlikely that a single factor can explain social segregation or habitat segregation but that a model

  7. Experimental determination of the segregation process using computer tomography

    Directory of Open Access Journals (Sweden)

    Konstantin Beckmann

    2016-08-01

    Full Text Available Modelling methods such as DEM and CFD are increasingly used for developing high efficient combine cleaning systems. For this purpose it is necessary to verify the complex segregation and separation processes in the combine cleaning system. One way is to determine the segregation and separation function using 3D computer tomography (CT. This method makes it possible to visualize and analyse the movement behaviour of the components of the mixture during the segregation and separation process as well as the derivation of descriptive process parameters. A mechanically excited miniature test rig was designed and built at the company CLAAS Selbstfahrende Erntemaschinen GmbH to achieve this aim. The investigations were carried out at the Fraunhofer Institute for Integrated Circuits IIS. Through the evaluation of the recorded images the segregation process is described visually. A more detailed analysis enabled the development of segregation and separation function based on the different densities of grain and material other than grain.

  8. Mass Segregation of Embedded Clusters in the Milky Way

    CERN Document Server

    Er, Xinyue; Fu, Yanning

    2012-01-01

    Embedded clusters are ideal laboratories to understand the early phase of the dynamical evolution of clusters as well as the massive star formation. An interesting observational phenomenon is that some of the embedded clusters show mass segregation, i.e., the most massive stars are preferentially found near the cluster center. In this paper, we develop a new approach to describe mass segregation. Using this approach and the Two Micron All Sky Survey Point Source Catalog (2MASS PSC), we analyze eighteen embedded clusters in the Galaxy. We find that eleven of them are mass-segregated and that the others are non-mass-segregated. No inversely mass-segregated cluster is found.

  9. Experimental determination of the segregation process using computer tomography

    Directory of Open Access Journals (Sweden)

    Konstantin Beckmann

    2016-07-01

    Full Text Available Modelling methods such as DEM and CFD are increasingly used for developing high efficient combine cleaning systems. For this purpose it is necessary to verify the complex segregation and separation processes in the combine cleaning system. One way is to determine the segregation and separation function using 3D computer tomography (CT. This method makes it possible to visualize and analyse the movement behaviour of the components of the mixture during the segregation and separation process as well as the derivation of descriptive process parameters. A mechanically excited miniature test rig was designed and built at the company CLAAS Selbstfahrende Erntemaschinen GmbH to achieve this aim. The investigations were carried out at the Fraunhofer Institute for Integrated Circuits IIS. Through the evaluation of the recorded images the segregation process is described visually. A more detailed analysis enabled the development of segregation and separation function based on the different densities of grain and material other than grain.

  10. Novel actin filaments from Bacillus thuringiensis form nanotubules for plasmid DNA segregation.

    Science.gov (United States)

    Jiang, Shimin; Narita, Akihiro; Popp, David; Ghoshdastider, Umesh; Lee, Lin Jie; Srinivasan, Ramanujam; Balasubramanian, Mohan K; Oda, Toshiro; Koh, Fujiet; Larsson, Mårten; Robinson, Robert C

    2016-03-01

    Here we report the discovery of a bacterial DNA-segregating actin-like protein (BtParM) from Bacillus thuringiensis, which forms novel antiparallel, two-stranded, supercoiled, nonpolar helical filaments, as determined by electron microscopy. The BtParM filament features of supercoiling and forming antiparallel double-strands are unique within the actin fold superfamily, and entirely different to the straight, double-stranded, polar helical filaments of all other known ParMs and of eukaryotic F-actin. The BtParM polymers show dynamic assembly and subsequent disassembly in the presence of ATP. BtParR, the DNA-BtParM linking protein, stimulated ATP hydrolysis/phosphate release by BtParM and paired two supercoiled BtParM filaments to form a cylinder, comprised of four strands with inner and outer diameters of 57 Å and 145 Å, respectively. Thus, in this prokaryote, the actin fold has evolved to produce a filament system with comparable features to the eukaryotic chromosome-segregating microtubule.

  11. Hybridization, transgressive segregation and evolution of new genetic systems in Drosophila

    Indian Academy of Sciences (India)

    H. A. Ranganath; S. Aruna

    2003-12-01

    Introgressive hybridization facilitates incorporation of genes from one species into the gene pool of another. Studies on long-term effects of introgressive hybridization in animal systems are sparse. Drosophila nasuta ($2n = 8$) and D. albomicans ($2n = 6$)—a pair of allopatric, morphologically almost identical, cross-fertile members of the nasuta subgroup of the immigrans species group—constitute an excellent system to analyse the impact of hybridization followed by transgressive segregation of parental characters in the hybrid progeny. Hybrid populations of D. nasuta and D. albomicans maintained for over 500 generations in the laboratory constitute new recombinant hybrid genomes, here termed cytoraces. The impact of hybridization, followed by introgression and transgressive segregation, on chromosomal constitution and karyotypes, some fitness parameters, isozymes, components of mating behaviour and mating preference reveals a complex pattern of interracial divergence among parental species and cytoraces. This assemblage of characters in different combinations in a laboratory hybrid zone allows us to study the emergence of new genetic systems. Here, we summarize results from our ongoing studies comparing these hybrid cytoraces with the parental species, and discuss the implications of these findings for our understanding of the evolution of new genetic systems.

  12. Segregation distortion of the CTG repeats at the myotonic dystrophy locus

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, R.; Stivers, D.N. [Univ. of Texas Houston Health Science Center, Houston, TX (United States); Deka, R.; Yu, Ling M.; Shriver, M.D.; Ferrell, R.E. [Univ. of Pittsburgh Graduate School of Public Health, Pittsburgh, PA (United States)

    1996-07-01

    Myotonic dystrophy (DM), an autosomal dominant neuromuscular disease, is caused by a CTG-repeat expansion, with affected individuals having {ge}50 repeats of this trinucleotide, at the DMPK locus of human chromosome 19q13.3. Severely affected individuals die early in life; the milder form of this disease reduces reproductive ability. Alleles in the normal range of CTG repeats are not as unstable as the (CTG){sub {ge}50} alleles. In the DM families, anticipation and parental bias of allelic expansions have been noted. However, data on mechanism of maintenance of DM in populations are conflicting. We present a maximum-likelihood model for examining segregation distortion of CTG-repeat alleles in normal families. Analyzing 726 meiotic events in 95 nuclear families from the CEPH panel pedigrees, we find evidence of preferential transmission of larger alleles (of size {le}29 repeats) from females (the probability of transmission of larger alleles is .565 {plus_minus} 0.03, different from .5 at P {approx} .028). There is no evidence of segregation distortion during male meiosis. We propose a hypothesis that preferential transmission of larger CTG-repeat alleles during female meiosis can compensate for mutational contraction of repeats within the normal allelic size range, and reduced viability and fertility of affected individuals. Thus, the pool of premutant alleles at the DM locus can be maintained in populations, which can subsequently mutate to the full mutation status to give rise to DM. 31 refs., 1 fig., 5 tabs.

  13. Effects of segregation of primary alloying elements on the creep response in magnesium alloys

    DEFF Research Database (Denmark)

    Huang, Y.D.; Dieringa, H.; Hort, N.

    2008-01-01

    The segregation of primary alloying elements deteriorates the high temperature creep resistance of magnesium alloys. Annealing at high temperatures alleviating their segregations can improve the creep resistance. Present investigation on the effect of segregation of primary alloying elements...

  14. Genetics of dioecy and causal sex chromosomes in plants

    Indian Academy of Sciences (India)

    Sushil Kumar; Renu Kumari; Vishakha Sharma

    2014-04-01

    Dioecy (separate male and female individuals) ensures outcrossing and is more prevalent in animals than in plants. Although it is common in bryophytes and gymnosperms, only 5% of angiosperms are dioecious. In dioecious higher plants, flowers borne on male and female individuals are, respectively deficient in functional gynoecium and androecium. Dioecy is inherited via three sex chromosome systems: XX/XY, XX/X0 and WZ/ZZ, such that XX or WZ is female and XY, X0 or ZZ are males. The XX/XY system generates the rarer XX/X0 andWZ/ZZ systems. An autosome pair begets XY chromosomes. A recessive loss-of-androecium mutation (ana) creates X chromosome and a dominant gynoecium-suppressing (GYS) mutation creates Y chromosome. The ana/ANA and gys/GYS loci are in the sex-determining region (SDR) of the XY pair. Accumulation of inversions, deleterious mutations and repeat elements, especially transposons, in the SDR of Y suppresses recombination between X and Y in SDR, making Y labile and increasingly degenerate and heteromorphic from X. Continued recombination between X and Y in their pseudoautosomal region located at the ends of chromosomal arms allows survival of the degenerated Y and of the species. Dioecy is presumably a component of the evolutionary cycle for the origin of new species. Inbred hermaphrodite species assume dioecy. Later they suffer degenerate-Y-led population regression. Cross-hybridization between such extinguishing species and heterologous species, followed by genome duplication of segregants from hybrids, give rise to new species.

  15. Mitotic chromosome biorientation in fission yeast is enhanced by dynein and a minus-end-directed, kinesin-like protein.

    Science.gov (United States)

    Grishchuk, Ekaterina L; Spiridonov, Ilia S; McIntosh, J Richard

    2007-06-01

    Chromosome biorientation, the attachment of sister kinetochores to sister spindle poles, is vitally important for accurate chromosome segregation. We have studied this process by following the congression of pole-proximal kinetochores and their subsequent anaphase segregation in fission yeast cells that carry deletions in any or all of this organism's minus end-directed, microtubule-dependent motors: two related kinesin 14s (Pkl1p and Klp2p) and dynein. None of these deletions abolished biorientation, but fewer chromosomes segregated normally without Pkl1p, and to a lesser degree without dynein, than in wild-type cells. In the absence of Pkl1p, which normally localizes to the spindle and its poles, the checkpoint that monitors chromosome biorientation was defective, leading to frequent precocious anaphase. Ultrastructural analysis of mutant mitotic spindles suggests that Pkl1p contributes to error-free biorientation by promoting normal spindle pole organization, whereas dynein helps to anchor a focused bundle of spindle microtubules at the pole.

  16. Intraspecific chromosome variability

    Directory of Open Access Journals (Sweden)

    N Dubinin

    2010-12-01

    Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title “Genetics and the origin of species”, and in the shadow of this American ‘skybuilding’ all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors’ version with the only addition being the reference list in the originally printed form.

  17. Sgo1 regulates both condensin and Ipl1/Aurora B to promote chromosome biorientation.

    Directory of Open Access Journals (Sweden)

    Karolina Peplowska

    2014-06-01

    Full Text Available Correct chromosome segregation is essential in order to prevent aneuploidy. To segregate sister chromatids equally to daughter cells, the sisters must attach to microtubules emanating from opposite spindle poles. This so-called biorientation manifests itself by increased tension and conformational changes across kinetochores and pericentric chromatin. Tensionless attachments are dissolved by the activity of the conserved mitotic kinase Aurora B/Ipl1, thereby promoting the formation of correctly attached chromosomes. Recruitment of the conserved centromeric protein shugoshin is essential for biorientation, but its exact role has been enigmatic. Here, we identify a novel function of shugoshin (Sgo1 in budding yeast that together with the protein phosphatase PP2A-Rts1 ensures localization of condensin to the centromeric chromatin in yeast Saccharomyces cerevisiae. Failure to recruit condensin results in an abnormal conformation of the pericentric region and impairs the correction of tensionless chromosome attachments. Moreover, we found that shugoshin is required for maintaining Aurora B/Ipl1 localization on kinetochores during metaphase. Thus, shugoshin has a dual function in promoting biorientation in budding yeast: first, by its ability to facilitate condensin recruitment it modulates the conformation of the pericentric chromatin. Second, shugoshin contributes to the maintenance of Aurora B/Ipl1 at the kinetochore during gradual establishment of bipolarity in budding yeast mitosis. Our findings identify shugoshin as a versatile molecular adaptor that governs chromosome biorientation.

  18. Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): comparisons with human and mouse

    DEFF Research Database (Denmark)

    Khlebodarova, TM; Malchenko, Sergey; Matveeva, NM;

    1995-01-01

    Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of mink-rodent hybrid cells. Analysis of segregation...

  19. Chromosome landing at the ¤Mla¤ locus in barley (¤Hordeum vulgare¤ L.) by means of high-resolution mapping with AFLP markers

    DEFF Research Database (Denmark)

    Schwarz, G.; Michalek, W.; Mohler, V.

    1999-01-01

    to construct a high-resolution map of the Mla region. A fluorescence-based AFLP technique and bulked segregant analysis were applied to screen for polymorphic, tightly linked AFLP markers, Three AFLP markers were selected as suitable for a chromosome-landing strategy. One of these AFLP markers and a closely...

  20. More reliable inference for the dissimilarity index of segregation.

    Science.gov (United States)

    Allen, Rebecca; Burgess, Simon; Davidson, Russell; Windmeijer, Frank

    2015-02-01

    The most widely used measure of segregation is the so-called dissimilarity index. It is now well understood that this measure also reflects randomness in the allocation of individuals to units (i.e. it measures deviations from evenness, not deviations from randomness). This leads to potentially large values of the segregation index when unit sizes and/or minority proportions are small, even if there is no underlying systematic segregation. Our response to this is to produce adjustments to the index, based on an underlying statistical model. We specify the assignment problem in a very general way, with differences in conditional assignment probabilities underlying the resulting segregation. From this, we derive a likelihood ratio test for the presence of any systematic segregation, and bias adjustments to the dissimilarity index. We further develop the asymptotic distribution theory for testing hypotheses concerning the magnitude of the segregation index and show that the use of bootstrap methods can improve the size and power properties of test procedures considerably. We illustrate these methods by comparing dissimilarity indices across school districts in England to measure social segregation.

  1. Ionic Segregation on Grain Boundaries in Thermally Grown Alumina Scales

    Energy Technology Data Exchange (ETDEWEB)

    Pint, Bruce A [ORNL; Unocic, Kinga A [ORNL

    2012-01-01

    This study first examined segregation behaviour in the alumina scale formed after 100 h at 1100 C on bare and MCrAlYHfSi-coated single-crystal superalloys with {approx}10 ppma La and Y. For the bare superalloy, Hf and Ti were detected on the grain boundaries of the inner columnar alumina layer. Increasing the oxidation temperature to 1200 C for 2 h did not change the segregation behavior. With the bond coating, both Y and Hf were segregated to the grain boundaries as expected. However, there was evidence of Ti-rich oxide particles near the gas interface suggesting that Ti diffused from the superalloy through the coating. To further understand these segregation observations with multiple dopants, other alumina-forming systems were examined. Alumina scale grain boundary co-segregation of Ti with Y is common for FeCrAl alloys. Co-segregation of Hf and Ti was observed in the scale formed on co-doped NiAl. No La segregation was detected in the scale formed on NiCrAl with only a 19 ppma La addition, however, the scale was adherent.

  2. Segregation and layering in the flow of wet granular matter

    Science.gov (United States)

    Samadani, Azadeh; Kudrolli, Arshad

    2000-11-01

    We report the effect of interstitial fluid on the extent of segregation by imaging the pile that results after bidisperse color-coded glass particles are poured into a silo. Segregation is sharply reduced and the angle of repose increases when a small volume fraction of fluid is added. The phase diagram of segregation as a function of volume fraction of the fluid and the size ratio of the particles is obtained. We also find that viscous forces in addition to capillary forces have an important effect on the extent of segregation and the angle of repose. We show that the sharp initial change and the subsequent saturation in the extent of segregation and angle of repose occurs over similar volume fraction of the fluid. Preferential clumping of small particles causes layering to occur when the size of the clumps of small particles exceeds the size of smoother large particles. We calculate the azimuthal correlation function of particle density inside the pile to characterize the layering. Finally the progress of segregation in the limit where particles are completely immersed in a fluid was measured. In this case liquid bridges and capillary forces are absent but viscous forces are present. We find that a transition back to segregation can occur when the particles are completely immersed in a fluid at low viscosities.

  3. Taylor revisited: Gender segregation and division of labour in the ICT - sector (information and communication technology)

    DEFF Research Database (Denmark)

    Nygaard, Else

    2001-01-01

    Information and communication technology, division of labour, gender segregation, working conditions......Information and communication technology, division of labour, gender segregation, working conditions...

  4. Evaluation of D1 and D2 dopamine receptor segregation in the developing striatum using BAC transgenic mice.

    Directory of Open Access Journals (Sweden)

    Dominic Thibault

    Full Text Available The striatum is predominantly composed of medium spiny neurons (MSNs that send their axons along two parallel pathways known as the direct and indirect pathways. MSNs from the direct pathway express high levels of D1 dopamine receptors, while MSNs from the indirect pathway express high levels of D2 dopamine receptors. There has been much debate over the extent of colocalization of these two major dopamine receptors in MSNs of adult animals. In addition, the ontogeny of the segregation process has never been investigated. In this paper, we crossed bacterial artificial chromosome drd1a-tdTomato and drd2-GFP reporter transgenic mice to characterize these models and estimate D1-D2 co-expression in the developing striatum as well as in striatal primary cultures. We show that segregation is already extensive at E18 and that the degree of co-expression further decreases at P0 and P14. Finally, we also demonstrate that cultured MSNs maintain their very high degree of D1-D2 reporter protein segregation, thus validating them as a relevant in vitro model.

  5. Mass Segregation in the Galactic Centre

    CERN Document Server

    Hopman, Clovis

    2010-01-01

    Two-body energy exchange between stars orbiting massive black holes (MBHs) leads to the formation of a power-law density distribution n(r)~r^(-a) that diverges towards the MBH. For a single mass population, a=7/4 and the flow of stars is much less than N(segregation with the use of Fokker-Planck calculations, and show that steady state is reached in 0.2-0.3 t_r. Since the relaxation time in the Galactic centre (GC) is t_r ~2-3 * 10^(10) yr, a cusp should form in less than a Hubble time. The absence of a visible cusp of old stars in the GC poses a challenge to these models, ...

  6. Itokawa: a case for ballistic segregation

    Science.gov (United States)

    Shinbrot, Troy; Sabawula, Tapan; Siu, Theo; Vivar Lazo, Miguel; Chakraborty, Pinaki

    Recent photographs of the asteroid Itokawa have revealed strong separation between regions populated almost entirely by small pebbles and other regions consisting only of larger boulders. This size separation has been attributed to the Brazil Nut Effect (BNE), however we point out here that the BNE depends on conditions such as isotropic gravity, parallel sidewalls and periodic vertical shaking that are wholly absent on asteroids. On the other hand, surface areas of boulders and pebbles appear to be comparable on Itokawa, and in this situation it follows that the asteroid must have suffered many orders of magnitude more collisions with pebbles than with boulders. We observe that a pebble will tend to bounce off of a boulder but will sink into a sea of similar pebbles, and so we predict that seas of pebbles must grow on such asteroids. We carry out experiments and simulations to evaluate this and related predictions, and we demonstrate that this new mechanism of segregation based on simple counting of grains can produce the strong separation of sizes reported. Support provided by NSF Grant 1404792.

  7. Urban Segregation with Cheap and Expensive Residences

    Science.gov (United States)

    Sumour, M. A.; El-Astal, A. H.; Radwan, M. A.; Shabat, M. M.

    In this paper we study urban segregation of two different communities A and B, rich and poor, distributed randomly on finite samples, to check cheap and expensive residences. For this purpose we avoid the complications of the Schelling model which are not necessary and instead we use the Ising model on 500 × 500 square lattices, which gives similar results, with random magnetic field at lower and higher temperatures (kBT/J = 2.0, 99.0) in finite times equal to 40, 400, 4000 and 40 000. This random-field Ising magnet is a suitable model, where each site of the square lattice carries a magnetic field ±h which is randomly up (expensive) or down (cheap). The resulting addition to the energy prefers up-spins on the expensive and down-spins on the cheap sites. Our simulations were carried out using a 50-line FORTRAN program. We present at a lower temperature (2.0) a time series of pictures, separating growing from non-growing domains. A small random field (h = ±0.1) allows for large domains, while a large random field (h = ±0.9) allows only small clusters. At higher temperature (99.0) we could not obtain growing domains.

  8. Charge segregation in weakly ionized microgels

    Science.gov (United States)

    Hyatt, John S.; Douglas, Alison M.; Stanley, Chris; Do, Changwoo; Barker, Thomas H.; Fernández-Nieves, Alberto

    2017-01-01

    We investigate microgels synthesized from N -isopropylacrylamide (NIPAM) copolymerized with a large mol% of acrylic acid, finding that when the acid groups are partially ionized at high temperatures, competition between ion-induced swelling and hydrophobic deswelling of poly(NIPAM) chains results in microphase separation. In cross-linked microgels, this manifests as a dramatic decrease in the ratio between the radius of gyration and the hydrodynamic radius to ˜0.2 , indicating that almost all the mass of the microgel is concentrated near the particle center. We also observe a concurrent decrease of the polymer network length scale via small-angle neutron scattering, confirming the presence of a dense, deswollen core surrounded by a diffuse, charged periphery. We compare these results to those obtained for a system of charged ultralow-cross-linked microgels; the form factor shows a distinct peak at high q when the temperature exceeds a threshold value. We successfully fit the form factor to theory developed to describe scattering from weakly charged gels in poor solvents, and we tie this behavior to charge segregation in the case of the cross-linked microgels.

  9. Double partial trisomy of 6p23-pter and 9pter-q21.2 in a neonate resulting from 4:2 meiotic segregation of a maternal complex t(6;7;9)(p23;p15;q21.2) translocation.

    Science.gov (United States)

    Cetin, Z; Mihci, E; Keser, I; Karaali, K; Berker, S; Luleci, G

    2012-01-01

    We report, a newborn presenting multiple congenital abnormalities with karyotype; 47,XY,der(7)t(6;7)(pter-p23::p15-->qter),+der(9)t(7;9)(pter-->p15::q21.2--> pter)t(6;7;9)(p23;p15;q21.2)mat[20]. The mother and her phenotypically normal daughter were carriers of a complex chromosomal rearrangement with karyotypes; 46,XX,t(6;7;9)(p23;p15;q21.2)[20]. Paternal chromosomes were normal. In our case the extra derivative chromosome was the result of a 4:2 segregation of the chromosomes involved in translocation during oogenesis. Double partial trisomy in newborns resulting from 4:2 segregation is a rare event, and double partial trisomies of the 6p23-pter and trisomy 9pter-q22 regions have not reported to date.

  10. The bacterial chromosome: architecture and action of bacterial SMC and SMC-like complexes.

    Science.gov (United States)

    Nolivos, Sophie; Sherratt, David

    2014-05-01

    Structural Maintenance of Chromosomes (SMC) protein complexes are found in all three domains of life. They are characterized by a distinctive and conserved architecture in which a globular ATPase 'head' domain is formed by the N- and C-terminal regions of the SMC protein coming together, with a c. 50-nm-long antiparallel coiled-coil separating the head from a dimerization 'hinge'. Dimerization gives both V- and O-shaped SMC dimers. The distinctive architecture points to a conserved biochemical mechanism of action. However, the details of this mechanism are incomplete, and the precise ways in which this mechanism leads to the biological functions of these complexes in chromosome organization and processing remain unclear. In this review, we introduce the properties of bacterial SMC complexes, compare them with eukaryotic complexes and discuss how their likely biochemical action relates to their roles in chromosome organization and segregation.

  11. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Directory of Open Access Journals (Sweden)

    Veronica eKrenn

    2015-10-01

    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  12. Chromosome Connections: Compelling Clues to Common Ancestry

    Science.gov (United States)

    Flammer, Larry

    2013-01-01

    Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…

  13. Chromosomal rearrangement interferes with meiotic X chromosome inactivation.

    Science.gov (United States)

    Homolka, David; Ivanek, Robert; Capkova, Jana; Jansa, Petr; Forejt, Jiri

    2007-10-01

    Heterozygosity for certain mouse and human chromosomal rearrangements is characterized by the incomplete meiotic synapsis of rearranged chromosomes, by their colocalization with the XY body in primary spermatocytes, and by male-limited sterility. Previously, we argued that such X-autosomal associations could interfere with meiotic sex chromosome inactivation. Recently, supporting evidence has reported modifications of histones in rearranged chromosomes by a process called the meiotic silencing of unsynapsed chromatin (MSUC). Here, we report on the transcriptional down-regulation of genes within the unsynapsed region of the rearranged mouse chromosome 17, and on the subsequent disturbance of X chromosome inactivation. The partial transcriptional suppression of genes in the unsynapsed chromatin was most prominent prior to the mid-pachytene stage of primary spermatocytes. Later, during the mid-late pachytene, the rearranged autosomes colocalized with the XY body, and the X chromosome failed to undergo proper transcriptional silencing. Our findings provide direct evidence on the MSUC acting at the mRNA level, and implicate that autosomal asynapsis in meiosis may cause male sterility by interfering with meiotic sex chromosome inactivation.

  14. Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes.

    Science.gov (United States)

    Gui, Liming; Homer, Hayden

    2012-06-01

    The spindle assembly checkpoint (SAC) averts aneuploidy by coordinating proper bipolar chromosomal attachment with anaphase-promoting complex/cyclosome (APC/C)-mediated securin and cyclin B1 destruction required for anaphase onset. The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition. During mitosis, kinetochores of polar-displaced chromosomes, which are at greatest risk of mis-segregating, recruit the highest levels of Mad2, thereby ensuring that SAC activation is proportionate to aneuploidy risk. Paradoxically, although an SAC operates in mammalian oocytes, meiosis I (MI) is notoriously error prone and polar-displaced chromosomes do not prevent anaphase onset. Here we find that Mad2 is not preferentially recruited to the kinetochores of polar chromosomes of wild-type mouse oocytes, in which polar chromosomes are rare, or of oocytes depleted of the kinesin-7 motor CENP-E, in which polar chromosomes are more abundant. Furthermore, in CENP-E-depleted oocytes, although polar chromosomal displacement intensified during MI and the capacity to form stable end-on attachments was severely compromised, all kinetochores nevertheless became devoid of Mad2. Thus, it is possible that the ability of the SAC to robustly discriminate chromosomal position might be compromised by the propensity of oocyte kinetochores to become saturated with unproductive attachments, thereby predisposing to aneuploidy. Our data also reveal novel functions for CENP-E in oocytes: first, CENP-E stabilises BubR1, thereby impacting MI progression; and second, CENP-E mediates bi-orientation by promoting kinetochore reorientation and preventing chromosomal drift towards the poles.

  15. Comparative genetic mapping points to different sex chromosomes in sibling species of wild strawberry (Fragaria).

    Science.gov (United States)

    Goldberg, Margot T; Spigler, Rachel B; Ashman, Tia-Lynn

    2010-12-01

    Separate sexes have evolved repeatedly from hermaphroditic ancestors in flowering plants, and thus select taxa can provide unparalleled insight into the evolutionary dynamics of sex chromosomes that are thought to be shared by plants and animals alike. Here we ask whether two octoploid sibling species of wild strawberry--one almost exclusively dioecious (males and females), Fragaria chiloensis, and one subdioecious (males, females, and hermaphrodites), F. virginiana--share the same sex-determining chromosome. We created a genetic map of the sex chromosome and its homeologs in F. chiloensis and assessed macrosynteny between it and published maps of the proto-sex chromosome of F. virginiana and the homeologous autosome of hermaphroditic diploid species. Segregation of male and female function in our F. chiloensis mapping population confirmed that linkage and dominance relations are similar to those in F. virginiana. However, identification of the molecular markers most tightly linked to the sex-determining locus in the two octoploid species shows that, in both, this region maps to homeologues of chromosome 6 in diploid congeners, but is located at opposite ends of their respective chromosomes.

  16. A comparison of male and female recombination frequency in wheat using RFLP maps of homoeologous group 6 and 7 chromosomes.

    Science.gov (United States)

    Wang, G; Hyne, V; Chao, S; Gale, M D; Henry, Y; De Buyser, J; Snape, J W

    1995-10-01

    A novel approach was used to compare male and female recombination rates in wheat. Doubled haploid lines were developed from an F1 using two distinct approaches: the anther-culture technique and the Hordeum bulbosum system, from which sets of lines were developed from "male" and "female" meioses, respectively. The genotype of the lines was established at RFLP and isozyme markers polymorphic on chromosomes of homoeologous groups 6 and 7, and "male" and "female" linkage maps were calculated using this information. The markers in one segment of chromosome 6B exhibited disturbed segregation frequencies in the anther-culture population. The "male" and "female" maps differed significantly in recombination frequency between some markers on two chromosomes, and these were consistent in direction within chromosomes and inconsistent in direction between chromosomes. In two of the four chromosomes studied the "male" map was much longer than the "female" map. These results suggest that significant differences may exist in male and female recombination frequencies in bread wheat which are specific to certain chromosomal segments but are inconsistent in direction between chromosomes. Other factors, such as environmental influences, may also be important in creating differences.

  17. Differing requirements for RAD51 and DMC1 in meiotic pairing of centromeres and chromosome arms in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Olivier Da Ines

    Full Text Available During meiosis homologous chromosomes pair, recombine, and synapse, thus ensuring accurate chromosome segregation and the halving of ploidy necessary for gametogenesis. The processes permitting a chromosome to pair only with its homologue are not fully understood, but successful pairing of homologous chromosomes is tightly linked to recombination. In Arabidopsis thaliana, meiotic prophase of rad51, xrcc3, and rad51C mutants appears normal up to the zygotene/pachytene stage, after which the genome fragments, leading to sterility. To better understand the relationship between recombination and chromosome pairing, we have analysed meiotic chromosome pairing in these and in dmc1 mutant lines. Our data show a differing requirement for these proteins in pairing of centromeric regions and chromosome arms. No homologous pairing of mid-arm or distal regions was observed in rad51, xrcc3, and rad51C mutants. However, homologous centromeres do pair in these mutants and we show that this does depend upon recombination, principally on DMC1. This centromere pairing extends well beyond the heterochromatic centromere region and, surprisingly, does not require XRCC3 and RAD51C. In addition to clarifying and bringing the roles of centromeres in meiotic synapsis to the fore, this analysis thus separates the roles in meiotic synapsis of DMC1 and RAD51 and the meiotic RAD51 paralogs, XRCC3 and RAD51C, with respect to different chromosome domains.

  18. Localization of introduced genes on the chromosomes of transgenic barley, wheat and triticale by fluorescence in situ hybridization

    DEFF Research Database (Denmark)

    Pedersen, C.; Zimny, J.; Becker, D.

    1997-01-01

    transformant showed a totally different integration pattern. Southern analysis confirmed that the inserted genes were segregating independently, resulting in different integration patterns among the progeny lines. The application of the FISH technique for the analysis of transgenic plants is discussed.......Using fluorescence in situ hybridization (FISH) we localized introduced genes on metaphase chromosomes of barley, wheat, and triticale transformed by microprojectile bombardment of microspores and scutellar tissue with the pDB1 plasmid containing the uidA and bar genes. Thirteen integration sites...... of single-copy integrations. There was a slight tendency towards the localization of transgenes in distal chromosome regions. Using the GAA-satellite sequence for chromosome banding, the chromosomes containing the inserted genes were identified in most cases. Two barley lines derived from the same...

  19. Cohesin in determining chromosome architecture

    Energy Technology Data Exchange (ETDEWEB)

    Haering, Christian H., E-mail: christian.haering@embl.de [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: rolf.jessberger@tu-dresden.de [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)

    2012-07-15

    Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.

  20. Dynamics of Transformation from Segregation to Mixed Wealth Cities

    CERN Document Server

    Sahasranaman, Anand

    2016-01-01

    We model the dynamics of the Schelling model for agents described simply by a continuously distributed variable - wealth. Agents move to neighborhoods where their wealth is not lesser than that of some proportion of their neighbors, the threshold level. As in the case of the classic Schelling model where segregation obtains between two races, we find here that wealth-based segregation occurs and persists. However, introducing uncertainty into the decision to move - that is, with some probability, if agents are allowed to move even though the threshold level condition is contravened - we find that even for small proportions of such disallowed moves, the dynamics no longer yield segregation but instead sharply transition into a persistent mixed wealth distribution. We investigate the nature of this sharp transformation between segregated and mixed states, and find that it is because of a non-linear relationship between allowed moves and disallowed moves. For small increases in disallowed moves, there is a rapid...