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Sample records for vzaimodejstvie chekpojnt-genov rad9

  1. Functional roles for Rad9 in prostate cancer

    International Nuclear Information System (INIS)

    Lieberman, H.B.; Broustas, C.G.

    2012-01-01

    The goal of this work is to understand the mechanistic relationship between high levels of Rad9 protein and prostate cancer. The study is based on several findings suggesting a role for Rad9 in this disease. Rad9 has all the hallmark features of an oncogene or tumor suppressor. It regulates genomic stability, multiple cell cycle checkpoints, apoptosis and DNA repair. In addition, it can transactivate downstream target genes via direct interaction with promoter DNA sequences. We found Rad9 protein levels were very high in prostate cancer cell lines. Furthermore, we examined 52 primary normal prostate and 339 prostate cancer specimens for Rad9 protein by immunohistochemical staining. Statistical significance for Rad9 positive staining versus cancer, and stain intensity versus Stage were tested. We get a p-value of <0.001 when comparing percentage positive by cancer Stage, or stain intensity by cancer Stage. Based on these data, we sought to define the nature of the relationship between Rad9 and prostate cancer. We demonstrate that Rad9 acts as an oncogene in prostate cancer by playing a critical role in tumor formation in a mouse xenograph model. We also show that Rad9 is important for cellular phenotypes essential for metastasis, including tumor cell migration, invasion and resistance to programmed cell death after detachment from extracellular matrix. Therefore, Rad9 is critical for several aspects of prostate tumor progression, and could serve as a novel target for anti-cancer therapy

  2. Rad9 Has a Functional Role in Human Prostate Carcinogenesis

    Science.gov (United States)

    Zhu, Aiping; Zhang, Charles Xia; Lieberman, Howard B.

    2013-01-01

    Prostate cancer is currently the most common type of neoplasm found in American men, other than skin cancer, and is the second leading cause of cancer death in males. Because cell cycle checkpoint proteins stabilize the genome, the relationship of one such protein, Rad9, to prostate cancer was investigated. We found that four prostate cancer cell lines (CWR22, DU145, LNCaP, and PC-3), relative to PrEC normal prostate cells, have aberrantly high levels of Rad9 protein. The 3′-end region of intron 2 of Rad9 in DU145 cells is hypermethylated at CpG islands, and treatment with 5′-aza-2′-deoxycytidine restores near-normal levels of methylation and reduces Rad9 protein abundance. Southern blot analyses indicate that PC-3 cells contain an amplified Rad9 copy number. Therefore, we provide evidence that Rad9 levels are high in prostate cancer cells due at least in part to aberrant methylation or gene amplification. The effectiveness of small interfering RNA to lower Rad9 protein levels in CWR22, DU145, and PC-3 cells correlated with reduction of tumorigenicity in nude mice, indicating that Rad9 actively contributes to the disease. Rad9 protein levels were high in 153 of 339 human prostate tumor biopsy samples examined and detectable in only 2 of 52 noncancerous prostate tissues. There was a strong correlation between Rad9 protein abundance and cancer stage. Rad9 protein level can thus provide a biomarker for advanced prostate cancer and is causally related to the disease, suggesting the potential for developing novel diagnostic, prognostic, and therapeutic tools based on detection or manipulation of Rad9 protein abundance. PMID:18316588

  3. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

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    Kumano, Tomoyasu [Kanazawa Univ. (Japan). Graduate School of Medical Science

    2002-12-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

  4. Rad9 contribution to radiosensitivity and the G2 checkpoint in a DT40 cell line

    International Nuclear Information System (INIS)

    Kumano, Tomoyasu

    2002-01-01

    In fission yeast, the rad9 (radiation sensitive) gene was cloned from a mutant that is sensitive to ionizing radiation, ultraviolet and hydroxyurea. This gene has also been shown to be required for a DNA damage checkpoint. Orthologues of the rad9 gene have recently been identified in higher eukaryote cells including human. Here we generated Rad9 knockout (Rad9-/-) cells from the chicken B lymphocyte line DT40 to examine the role of Rad9 in higher eukaryotes. First we isolated a part of the chicken Rad9 gene which was 54% identical with human Rad9 at the amino acid sequence level. Next we isolated genomic clones, determined exons and introns, and constructed targeting vectors designed to disrupt exon 1-3 of the chicken Rad9 gene by replacement with a drug-resistant gene. Successful targeted integration was verified by Southern blot analysis and the disruption of the Rad9 gene was confirmed by reverse transcription polymerase chain reaction (RT-PCR). To analyze the radiosensitivity of these Rad9-/- cells, we monitored the clonogenic survival after various degrees of X-ray irradiation. Rad9-/- cells were more sensitive to X-rays than wild type cells at all dosages. However, these cells were less sensitive than ATM knockout (ATM-/-) cells that are known to be X-ray sensitive and that showed a defective checkpoint control. In contrast, Rad9-/- cells were markedly more sensitive to ultraviolet and hydroxyruea. In addition, we assessed the G2 checkpoint by measurement of the mitotic index that is the fraction of the accumulating number of cells in mitosis at various times after X-ray irradiation. While the number of mitotic wild type cells did not increase until 2 hrs after X-ray irradiation, the number of mitotic Rad9-/- cells showed an increase similar to that of ATM-/- cells. These results suggest that just as in fission yeast, in higher eukaryotes Rad9 also contributes to X-ray, ultraviolet and hydroxyurea sensitivity, and plays an important role in the G2 checkpoint

  5. Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage

    Science.gov (United States)

    Leloup, Corinne; Hopkins, Kevin M.; Wang, Xiangyuan; Zhu, Aiping; Wolgemuth, Debra J.; Lieberman, Howard B.

    2010-01-01

    RAD9 participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue of RAD9 (named RAD9B) has been identified. To define the function of mouse Rad9b (Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generate Mrad9b mutant mice. Mrad9b−/− embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth. Mrad9b is expressed in embryonic brain and Mrad9b+/− embryos exhibit abnormal neural tube closure. Mrad9b−/− mouse embryonic fibroblasts are not viable. Mrad9b−/− ES cells are more sensitive to gamma rays and mitomycin C than Mrad9b+/+ controls, but show normal gamma-ray-induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability in Mrad9b−/− cells. Our findings thus indicate that Mrad9b is essential for embryonic development and mediates resistance to certain DNA damaging agents. PMID:20842695

  6. RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response

    International Nuclear Information System (INIS)

    Ghandhi, Shanaz A; Ponnaiya, Brian; Panigrahi, Sunil K; Hopkins, Kevin M; Cui, Qingping; Hei, Tom K; Amundson, Sally A; Lieberman, Howard B

    2014-01-01

    Radiation induced bystander effects are an important component of the overall response of cells to irradiation and are associated with human health risks. The mechanism responsible includes intra-cellular and inter-cellular signaling by which the bystander response is propagated. However, details of the signaling mechanism are not well defined. We measured the bystander response of Mrad9 +/+ and Mrad9 −/− mouse embryonic stem cells, as well as human H1299 cells with inherent or RNA interference-mediated reduced RAD9 levels after exposure to 1 Gy α particles, by scoring chromosomal aberrations and micronuclei formation, respectively. In addition, we used microarray gene expression analyses to profile the transcriptome of directly irradiated and bystander H1299 cells. We demonstrated that Mrad9 null enhances chromatid aberration frequency induced by radiation in bystander mouse embryonic stem cells. In addition, we found that H1299 cells with reduced RAD9 protein levels showed a higher frequency of radiation induced bystander micronuclei formation, compared with parental cells containing inherent levels of RAD9. The enhanced bystander response in human cells was associated with a unique transcriptomic profile. In unirradiated cells, RAD9 reduction broadly affected stress response pathways at the mRNA level; there was reduction in transcript levels corresponding to genes encoding multiple members of the UVA-MAPK and p38MAPK families, such as STAT1 and PARP1, suggesting that these signaling mechanisms may not function optimally when RAD9 is reduced. Using network analysis, we found that differential activation of the SP1 and NUPR1 transcriptional regulators was predicted in directly irradiated and bystander H1299 cells. Transcription factor prediction analysis also implied that HIF1α (Hypoxia induced factor 1 alpha) activation by protein stabilization in irradiated cells could be a negative predictor of the bystander response, suggesting that local hypoxic stress

  7. RAD9, RAD17; RAD24, and RAD53 control one pathway of resistance to γ irradiation in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshina, M.P.; Devin, A.B.

    2009-01-01

    Mechanisms for the genetic control of the cell cycle transition (checkpoint control) have been studied in more detail in yeast Saccharomyces cerevisiae. To clarify tho role of the RAD9, RAD17, RAD24, and RAD53 checkpoint genes in cell radioresistance, diploid double mutants were analyzed for cell sensitivity to ionizing radiation. All mutations in combination with rad9Δ were shown to manifest the epistatic type of interaction. Our results suggest that the RAD9, RAD17, RAD24, and RAD53 checkpoint genes belong to a single epistasis group called the RAD9 group and participate in the same pathway. RAD9 and RAD53 have a positive effect on sensitivity to γ irradiation, whereas RAD17 and RAD24 have a negative effect. For haploid interactions between mutations may differ in the case of γ or UV irradiation, mutations - for example, rad9Δ and rad24Δ - were shown to have an additive effect in the first case and epistatic - in the second. The analyzed genes can also participate in minor mechanisms of radioresistance that are relatively independent of the above major mechanism

  8. Interactions of checkpoint-genes RAD9, RAD17, RAD24 and RAD53 determining radioresistance of Yeast Saccharomyces Cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Nikulushkina, Yu.V.; Roshchina, M.P.; Devin, A.B.

    2007-01-01

    The mechanisms of genetic control of progress through the division cell cycle (checkpoint-control) in yeast Saccharomyces cerevisiae have been studied intensively. To investigate the role of checkpoint-genes RAD9, RAD17, RAD24, RAD53 in cell radioresistance we have investigated cell sensitivity of double mutants to γ-ray. Double mutants involving various combinations with rad9Δ show epistatic interactions, i.e. the sensitivity of the double mutants to γ-ray was no greater than that of more sensitive of the two single mutants. This suggests that all these genes govern the same pathway. This group of genes was named RAD9-epistasis group. It is interesting to note that the genes RAD9 and RAD53 have positive effect but RAD17 and RAD24 have negative effect on radiosensitivity of yeast cells. Interactions between mutations may differ depending on the agent γ-ray or UV-light, for example mutations rad9Δ and rad24Δ show additive effect for γ-ray and epistatic effect for UV-light

  9. Phosphorylation of Rad9 at serine 328 by cyclin A-Cdk2 triggers apoptosis via interfering Bcl-xL.

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    Zhuo Zhan

    Full Text Available Cyclin A-Cdk2, a cell cycle regulated Ser/Thr kinase, plays important roles in a variety of apoptoticprocesses. However, the mechanism of cyclin A-Cdk2 regulated apoptosis remains unclear. Here, we demonstrated that Rad9, a member of the BH3-only subfamily of Bcl-2 proteins, could be phosphorylated by cyclin A-Cdk2 in vitro and in vivo. Cyclin A-Cdk2 catalyzed the phosphorylation of Rad9 at serine 328 in HeLa cells during apoptosis induced by etoposide, an inhibitor of topoisomeraseII. The phosphorylation of Rad9 resulted in its translocation from the nucleus to the mitochondria and its interaction with Bcl-xL. The forced activation of cyclin A-Cdk2 in these cells by the overexpression of cyclin A,triggered Rad9 phosphorylation at serine 328 and thereby promoted the interaction of Rad9 with Bcl-xL and the subsequent initiation of the apoptotic program. The pro-apoptotic effects regulated by the cyclin A-Cdk2 complex were significantly lower in cells transfected with Rad9S328A, an expression vector that encodes a Rad9 mutant that is resistant to cyclin A-Cdk2 phosphorylation. These findings suggest that cyclin A-Cdk2 regulates apoptosis through a mechanism that involves Rad9phosphorylation.

  10. Tousled-like kinase-dependent phosphorylation of Rad9 plays a role in cell cycle progression and G2/M checkpoint exit.

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    Ryan Kelly

    Full Text Available Genomic integrity is preserved by checkpoints, which act to delay cell cycle progression in the presence of DNA damage or replication stress. The heterotrimeric Rad9-Rad1-Hus1 (9-1-1 complex is a PCNA-like clamp that is loaded onto DNA at structures resulting from damage and is important for initiating and maintaining the checkpoint response. Rad9 possesses a C-terminal tail that is phosphorylated constitutively and in response to cell cycle position and DNA damage. Previous studies have identified tousled-like kinase 1 (TLK1 as a kinase that may modify Rad9. Here we show that Rad9 is phosphorylated in a TLK-dependent manner in vitro and in vivo, and that T355 within the C-terminal tail is the primary targeted residue. Phosphorylation of Rad9 at T355 is quickly reduced upon exposure to ionizing radiation before returning to baseline later in the damage response. We also show that TLK1 and Rad9 interact constitutively, and that this interaction is enhanced in chromatin-bound Rad9 at later stages of the damage response. Furthermore, we demonstrate via siRNA-mediated depletion that TLK1 is required for progression through S-phase in normally cycling cells, and that cells lacking TLK1 display a prolonged G2/M arrest upon exposure to ionizing radiation, a phenotype that is mimicked by over-expression of a Rad9-T355A mutant. Given that TLK1 has previously been shown to be transiently inactivated upon phosphorylation by Chk1 in response to DNA damage, we propose that TLK1 and Chk1 act in concert to modulate the phosphorylation status of Rad9, which in turn serves to regulate the DNA damage response.

  11. Human RAD18 interacts with ubiquitylated chromatin components and facilitates RAD9 recruitment to DNA double strand breaks.

    Directory of Open Access Journals (Sweden)

    Akiko Inagaki

    Full Text Available RAD18 is an ubiquitin ligase involved in replicative damage bypass and DNA double-strand break (DSB repair processes. We found that RPA is required for the dynamic pattern of RAD18 localization during the cell cycle, and for accumulation of RAD18 at sites of γ-irradiation-induced DNA damage. In addition, RAD18 colocalizes with chromatin-associated conjugated ubiquitin and ubiquitylated H2A throughout the cell cycle and following irradiation. This localization pattern depends on the presence of an intact, ubiquitin-binding Zinc finger domain. Using a biochemical approach, we show that RAD18 directly binds to ubiquitylated H2A and several other unknown ubiquitylated chromatin components. This interaction also depends on the RAD18 Zinc finger, and increases upon the induction of DSBs by γ-irradiation. Intriguingly, RAD18 does not always colocalize with regions that show enhanced H2A ubiquitylation. In human female primary fibroblasts, where one of the two X chromosomes is inactivated to equalize X-chromosomal gene expression between male (XY and female (XX cells, this inactive X is enriched for ubiquitylated H2A, but only rarely accumulates RAD18. This indicates that the binding of RAD18 to ubiquitylated H2A is context-dependent. Regarding the functional relevance of RAD18 localization at DSBs, we found that RAD18 is required for recruitment of RAD9, one of the components of the 9-1-1 checkpoint complex, to these sites. Recruitment of RAD9 requires the functions of the RING and Zinc finger domains of RAD18. Together, our data indicate that association of RAD18 with DSBs through ubiquitylated H2A and other ubiquitylated chromatin components allows recruitment of RAD9, which may function directly in DSB repair, independent of downstream activation of the checkpoint kinases CHK1 and CHK2.

  12. A Rad53 independent function of Rad9 becomes crucial for genome maintenance in the absence of the Recq helicase Sgs1.

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    Ida Nielsen

    Full Text Available The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses, replisome stability and dissolution of double Holliday junctions during homologous recombination. In this study we investigate a possible genetic interaction between SGS1 and RAD9 in the cellular response to methyl methane sulphonate (MMS induced damage and compare this with the genetic interaction between SGS1 and RAD24. The Rad9 protein, an adaptor for effector kinase activation, plays well-characterized roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a sensor protein also in the DNA damage checkpoint response. Here we unveil novel insights into the cellular response to MMS-induced damage. Specifically, we show a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS induced damage and for suppression of gross chromosomal rearrangements, which is not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU-induced checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3. Thus, whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU-induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3 together define a minor but parallel pathway to that of Rad9.

  13. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9.

    Directory of Open Access Journals (Sweden)

    Hien-Ping Ngo

    2010-08-01

    Full Text Available Maintenance of telomere capping is absolutely essential to the survival of eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively. Here we identify, for the first time, three genetic modifications that allow budding yeast cells to survive without telomere capping by Cdc13. We found that simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response (DDR proteins, is sufficient to allow cell division in the absence of Cdc13. Quantitative amplification of ssDNA (QAOS was used to show that the RecQ helicase Sgs1 plays an important role in the resection of uncapped telomeres, especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped telomeres and together with deletion of RAD9 permits cell survival without CDC13. Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Delta sgs1Delta exo1Delta strains can maintain linear chromosomes despite the absence of telomere capping by Cdc13. However, with continued passage, the telomeres of such strains eventually become short and are maintained by recombination-based mechanisms. Remarkably, cdc13Delta rad9Delta sgs1Delta exo1Delta strains, lacking any Cdc13 gene product, are viable and can grow indefinitely. Our work has uncovered a critical role for RecQ helicases in limiting the division of cells with uncapped telomeres, and this may provide one explanation for increased tumorigenesis in human diseases associated with mutations of RecQ helicases. Our results reveal the plasticity of the telomere cap and indicate that the essential role of telomere capping is to counteract specific aspects of the DDR.

  14. Repair of pyrimidine dimers in radiation-sensitive mutants rad3, rad4, rad6, and rad9 of Saccharomyces cerevisiae. [nicking

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    Prakash, L [Rochester Univ., N.Y. (USA). Dept. of Radiation Biology and Biophysics; Rochester Univ., N.Y. (USA). School of Medicine and Dentistry)

    1977-10-01

    The ability to remove ultraviolet-induced pyrimidine dimers was examined in four radiation-sensitive mutants of Saccharomyces cerevisiae. The susceptibility of DNA from irradiated cells to nicking by either the T4 uv-endonuclease or an endonuclease activity found in crude extracts of Micrococcus luteus was used to measure the presence of dimers in DNA. The rad3 and rad4 mutants are shown to be defective in dimer excision whereas the rad6 and rad9 mutants are proficient in dimer excision.

  15. TLK1 and Rad9 Cooperate in XRT-Refractory CaP

    Science.gov (United States)

    2011-04-01

    left with few options for establishing the role of such phosphorylation in higher organisms, in cell lines and even more importantly in transgenic ...Asf1 [12]. In this assay, Bluescript plasmid isolated from bacteria was first relaxed with wheat -germ Topoisomerase 1 (Figure 1 panel B, lane 5 and

  16. Interaction Between Hf Waves and Plasma in Delta-2; Interaction dans 'Delta-2' d'une Onde Progressive Electromagnetique de Haute Frequence et d'un Plasma; Vzaimodejstvie vysokochastotnoj ehlektromagnitnoj begushchej volny s plazmoj na ustanovke ''Del'ta-2'; Interaccion de una Onda Progresiva Electromagnetica de Alta Frecuencia con el Plasma en la Instalacion 'Delta-2'

    Energy Technology Data Exchange (ETDEWEB)

    Breus, S. N.; Kurdjumov, V. N.; Levin, M. L.; Osovec, S. M.; Popova, N. Ja.; Popov, I. A.; Hodataev, K. V.; Shimchuk, V. P. [Radiotehnicheskij Institut AN SSSR, Moskva, SSSR (Russian Federation)

    1966-04-15

    las corrientes transversales en el plasma. Este campo tiene una estructura compleja y, posiblemente, esta determinado, como indica una teorfa aproximada, por el efecto toroidal. La existencia de los campos magneticos cuasi-estacionarios guarda al parecer una relacion con las oscilaciones del plasma que se han observado, de 200 a 500 kHz, correspondientes, aproximadamente, a las oscilaciones de Alfven en dichos campos. La presencia de campos y de corrientes cuasi-estacionarios hace que sea mas diffcil separar el plasma de las paredes de la camara de descarga y lograr la constriccion ulterior. Sin embargo, las corrientes constantes axiales, por si mismas, no pueden dar lugar a la aparicion de inestabilidades del tipo cinetico, ya que las velocidades electronicas que les corresponden son menores que la velocidad de fase de la onda progresiva, la cual es, aproximadamente, igual a 5 * 10{sup 7} cm/s, es decir, apreciablemente menor que la velocidad termica de los electrones. (author) [Russian] Izlagajutsja rezul'taty issledovanija vzaimodejstvija plotnoj plazmy s vysokochastotnym polem magnitnoj volny, begushhej vdol' toroidal'noj razrjadnoj kamery (bol'shoj diametr - 700 mm, malyj - 85 mm). Begushhaja volna vozbuzhdaetsja na chastote f = 2,4 Mgc trehfaznym avtogeneratorom moshhnost'ju okolo 50 Mvt s dlitel'nost'ju impul'sa okolo 250 i 350 mksek. Pri jeksperimentah diapazon nachal'nyh davlenij sostavljal 0,1 - 0,001 tor, a amplituda vysokochastotnogo magnitnogo polja na poverhnosti plazmy dostigala 500-600 je. V jetih uslovijah osnovnye javlenija, opredeljajushhie vzaimodejstvie plazmy s polem begushhej volny, svjazany s nalichiem nelinejnyh jeffektov i, prezhde vsego, s pojavleniem postojannoj sostavljajushhej prodol'nogo toka, kotoraja dostigala znachenij neskol'kih tysjach amper. V centre kamery v oblasti malyh polej provodimost' plazmy byla porjadka (3 - 4)*10{sup 14} CGSE, chto pri stepeni ionizacii, blizkoj k 100%, sootvetstvuet jelektronnoj temperature 8 - 12 jev. V

  17. Reaction of pyridine-N-oxides with halogens; Vzaimodejstvie piridin-N-oksidov s galogenami

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    Kanibolotskij, A L; Mikhzajlov, V A; Savelova, V A [AN Ukrainskoj SSR, Donetsk (Ukraine). Inst. Fiziko-Organicheskoj Khimii i Uglekhimii

    1994-12-31

    By the methods of conductometry, NMR and IR spectroscopy it has been ascertained that interaction of pyridine-N-oxides with bromine, iodine and interhalides (ICl and IBr) gives rise to the formation of crystal complexes of 1:1 composition. The complexes mentioned are of presumably ionic structure: [RC{sub 5}H{sub 4}N-O...X...O-NC{sub 5}H{sub 4}R]{sup +}[Y-X-Y]{sup -},where X,Y = Cl,Br,I.

  18. A Rad53 Independent Function of Rad9 Becomes Crucial for Genome Maintenance in the Absence of the RecQ Helicase Sgs1

    DEFF Research Database (Denmark)

    Nielsen, Ida; Bentsen, Iben Bach; Andersen, Anni Hangaard

    2013-01-01

    becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU)-induced checkpoint responses with relation...

  19. Proceedings of the Fourth international conference 'Interaction of radiation with solids'; Materialy chetvertoj mezhdunarodnoj konferentsii 'Vzaimodejstvie izluchenij s tverdym telom'

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    Anishchik, V M [ed.; Zhukova, S I; Azarko, I I; Prikhod' ko, Zh L

    2001-10-01

    The 132 collected papers form the Proceedings of the International Conference 'Interaction of Radiation with Solids'. This Conference is the fourth forum biennially gathering in Minsk the specialists from different countries. The scope of the problems considered at the Conference is widening steadily from year to year including the recent results and most advanced leads in the field of radiation physics of condensed matter. In the proceedings consideration is being given to 'Processes of ion interaction with solids', 'Plasma interaction with surface' and 'Radiation effects in solids'.

  20. Reactions of vanadium(5) with aluminium(3) in weakly acid aqueous solutions; Vzaimodejstvie mezhdu vanadiem(5) i alyhminiem(3) v slabokislykh vodnykh rastvorakh

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    Ditrikh, I V; Makhno, A Ya [Donetskij Gosudarstvennyj Univ., Donetsk (Ukraine)

    1997-12-31

    Conditions of vanadium(5) heteropolycompounds formation in aqueous solutions containing aluminium(3) have been studied. By the methods of potentiometry and conductometry in solutions of Al(NO{sub 3}){sub 3}-NaVO{sub 3} salt mixture the formation of complexes with the ratios [Al{sup 3+}]:[V{sup 5+}]=1:3, 1:6 and 1:12 has been ascertained. A salt of gross formula 3NaO {center_dot} (Al{sub 2}){sub 3} {center_dot} 12V{sub 2}O{sub 5} {center_dot} 67H{sub 2}O has been isolated. 3 refs.; 2 figs.

  1. Study of leading neutral pions: (interactions of cosmic rays with matter at energies above 3 TeV). Izuchenie lidiruyushchikh nejtral'nykh pionov (vzaimodejstvie kosmicheskikh chastits s veshchestvom pri ehnergiyakh vyshe 3 TeV)

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    Eremenko, Yu A

    1988-01-01

    An experimental plant consisting of a full-automatic ionized colorimeter of 44m{sup 2}, electronics of which is based on modern integral schemes and performed in CAMAC standard; of an x-ray emulsion chamber and of changeable dense target is described. The plant permits to measure the energy of a primary particle, as well as to study in detail a neutral component of products of strong indifferent target atoms. Experimental data on leading neutral mesons with energy from 10 GeV to the cosmic particle energies are analysed using the plant. A new experiment, which aim is the detection of interactions with anomalously great multiplicity and study of microstructure of extensive air showers, is suggested. 277 refs.

  2. Beam-plasma interaction with an electron beam injecting into a symmetrically open plasma system; Electron beam relaxation. Puchkovo-plazmennoe vzaimodejstvie pri inzhektsii ehlektronnogo puchka v simmetrichno otkrytuyu plazmennuyu sistemu; Relaksatsiya ehlektronnogo puchka

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    Opanasenko, A V; Romanyuk, L I [AN Ukrainskoj SSR, Kiev (Ukrainian SSR). Inst. Yadernykh Issledovanij

    1989-10-01

    The relaxation of the electron beam with the electron density of 1-2 keV injected through the symmetrically open plasma system with the independent hot cathode Penning discharge is experimentally investigated. It is shown that the velocity distribution function of the electron beam changes after passing each wave generation zone induced by the beam. The contribution of different wave zones to the beam relaxation depends on the prehistory of the beam-plasma interaction and may be regulated by the selection of the plasma system parameters. By this way the complete relaxation of the electron beam can be achieved after the beam crossing the whole system.

  3. Interaction of zirconium and hafnium tetrachlorides with cesium, rubidium and potassium chlorides and Raman spectra of reaction products; Vzaimodejstvie tetrakhloridov tsirkoniya i gafniya s khloridami tseziya, rubidiya i kaliya i spektry KRS produktov reaktsij

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    Salyulev, A B; Vovkotrub, Eh G; Strekalovskij, V N [UrO RAN, Inst. Vysokotemperaturnoj Ehlektrokhimii, Ekaterinburg (Russian Federation)

    2008-05-15

    Raman spectroscopy was used to reveal the formation of novel complexes involving [Zr{sub 2}Cl{sub 9}]{sup -} and [Hf{sub 2}Cl{sub 9}]{sup -} anions in molten mixtures of ZrCl{sub 4} and HfCl{sub 4} with CsCl, RbCl, and KCl. A prediction is made about the presence of the above-mentioned complex anions in poorly investigated melts of the corresponding binary systems at high concentrations of ZrCl{sub 4} or HfCl{sub 4}.

  4. Interaction of phosphorus pentachloride with trichlorides of metals of the second half of lanthanide series and scandium subgroup; Vzaimodejstvie pentakhlorida fosfora s trikhloridami metallov vtoroj poloviny semejstva lantanidov i podgruppy skandiya

    Energy Technology Data Exchange (ETDEWEB)

    Salyulev, A B; Vovkotrub, Eh G; Strekalovskij, V N [Inst. Vysokotemperaturnoj Ehlektrokhimii UrO RAN, Ekaterinburg (Russian Federation)

    1999-02-01

    With the use of Raman laser spectroscopy a study is made into interactions of molten TbCl{sub 3}, ErCl{sub 3}, YbCl{sub 3}, YCl{sub 3} and ScCl{sub 3} with phosphorus pentachloride vapors at elevated pressure (up to 30-35 atm) as well as solid REM trichlorides with molten PCl{sub 5}. It is revealed for first time that the interaction can be accompanied by reactions resulting in formation of complex chloride cations [PCl{sub 4}]{sup +} and anions [MCl{sub 6}]{sup 3-} of trivalent metals. The prediction is made about the possibility of chemical interaction of phosphorus pentachloride with trichlorides of all yttrium subgroup lanthanides under similar conditions.

  5. Genetic Screens in Yeast to Identify BRCA1 Modifiers

    National Research Council Canada - National Science Library

    Plon, Sharon E

    2005-01-01

    .... The yeast RAD9 protein has similar functions and sequence motifs as BRCA1 and we proposed to identify haploinsufficient mutations at a second locus that alters the chromosome loss rate of our rad9-/- diploid strains...

  6. Book of abstracts of the 3rd International conference and the 3rd International School for young scientists Interaction of hydrogen isotopes with structural materials. IHISM-07; Tezisy dokladov Tret'ej mezhdunarodnoj konferentsii i Tret'ej mezhdunarodnoj Shkoly molodykh uchenykh i spetsialistov Vzaimodejstvie izotopov vodoroda s konstruktsionnymi materialami. IHISM-07

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    The book involves abstracts of presentations at the 3rd International Conference and the 3rd International School for Young Scientists Interaction of Hydrogen Isotopes with Structural Materials (IHISM-07). The activities of Russian and foreign scientific centers associated with the use of hydrogen isotopes in power engineering, national economy and basic research are considered. The presentations cover the following areas: kinetics and interaction between hydrogen isotopes and solids including effects of radiogenic helium accumulation, hydrides and hydride transformations; structural transformations and mechanical properties; equipment and research techniques.

  7. The Interaction of C{sup 14} Recoil Atoms in Binary Mixtures; Interaction entre Atomes {sup 14}C de Recul et Composants de Melanges Binaires; Vzaimodejstvie atomov otdachi ugleroda-14 v binarnykh smesyakh; Interaccion de los Atomos de Retroceso del {sup 14}C en Mezclas Binarias

    Energy Technology Data Exchange (ETDEWEB)

    Firsova, L. P.; Barakat, M. F.; Forys, M.; Nesmejanov, An. N. [Moskovskij Gosudarstvennyj Universitet, Moskva, SSSR (Russian Federation)

    1965-04-15

    A study was made of the intermolecular distribution of activity in C{sup 14} -labelled products, formed as a result of the interaction of C{sup 14} atoms with components of binary liquid mixtures containing heterocyclic compounds. Particular attention was paid to the systems indole-aniline, indole-pyridine, {alpha}-picoline-toluene, {alpha}-picolene-aniline, etc. Data were obtained on the relation between the radiochemical yields of labelled products and the concentration of components in dilute solutions and in comparable concentrations of substances in mixtures. Analysis of the experimental results for an additive system enabled us to determine the deviations from the additivity principle. The deviations observed were interpreted as the result of the participation of the second component of the system in the primary and secondary reactions accompanying nuclear transformations. In considering the role of the second component, we took into account the variations in its predominant reaction mechanisms in various concentration ranges. Special attention was paid to the possibility of an intermolecular transfer of the energy of a radiation shield, and also of the mechanism of the corresponding processes. (author) [French] Les auteurs etudient la distribution intermoleculaire de la radioactivite dans les produits marques avec {sup 14}C qui se forment a la suite de l'interaction entre le carbone-14 et les composants de melanges liquides binaires contenant des substances heterocycliqiies. Ils examinent notamment les systemes indole-aniline, indole- pyxidine, {alpha}-picoline-toluol, {alpha}-picoline-aniline, etc. Ils ont obtenu des donnees sur la relation entre le rendement radiochimique en produits marques et la concentration des composants pour des solutions diluees et pour des melanges ou les deux substances ont des concentrations comparables. En traitant les donnees experimentales selon un schema additif, ils ont constate des ecarts par rapport a la regle d'additivite. Ces ecarts sont consideres comme resultant du fait que le deuxieme composant du systeme participe aux reactions primaires et secondaires qui accompagnent les transformations nucleaires. En examinant le role du deuxieme composant, les auteurs tiennent compte des particularites que presentent les mecanismes dominants des reactions subies par ce composant dans les divers intervalles de concentration. Ils etudient notamment la possibilite.d'un transfert d'energie intermoleculaire, ainsi que les mecanismes des processus correspondants. (author) [Spanish] Los autores han investigado la distribucion intermolecular de la actividad en los productos marcados con {sup 14}C, formados como resultado de la interaccion de atomos de {sup 14}C con los componentes de mezclas binarias en estado liquido que contienen compuestos heterociclicos. Prestaron particular atencion a los sistemas indol-anilina, indol-piridina, {alpha}-picolina-tolueno, {alpha}-picolina-anilina, etc. Obtuvieron datos sobre los rendimientos radioquimicos de los productos marcados en funcion de la concentracion de los componentes en soluciones diluidas y en mezclas con concentraciones comparables de sustancias. El analisis de los resultados experimentales correspondientes a un sistema de adicion, permitio a los autores determinar las desviaciones con respecto a la normal. Estas desviaciones se consideraron como resultado de la participacion de un segundo componente del sistema en las reacciones primarias y secundarias que acompanan a las transformaciones nucleares. Al examinar el papel desempenado por el segundo componente, tuvieron en cuenta la variacion de los mecanismos de reaccion predominantes en distintos intervalos de concentracion. Examinaron en particular la posibilidad de una transferencia intermolecular de la energfa de resistencia a la radiolisis, asi como los mecanismos de los procesos correspondientes. (author) [Russian] Issledovano mezhmolekuljarnoe raspredelenie aktivnosti v mechennyhpo C{sup 14} produktah, obrazujushhihsja v rezul'tate vzaimodejstvija atomov ugleroda-14 s komponentami binarnyh zhidkih smesej, soderzhashhih geterociklicheskie soedinenija. V chastnosti, izucheny sistemy indol- anilin, indol- piridin, {alpha}-pikolin -toluol, {alpha}-pikolin-anilin i t.d. Polucheny dannye po zavisimosti radiohimicheskih vyhodov mechenyh produktov ot koncentracii komponentov v oblasti razbavlennyh rastvorov i v oblasti sravnimyh koncentracij veshhestv v smesjah. Pri obrabotke jeksperimental'nyh rezul'tatov po additivnoj sheme bshsh zafiksirovany otklonenija ot pravila additivnosti. Nabljudavshiesja otklonenija traktujutsja kak rezul'tat uchastija vtorogo komponenta sistemy v pervichnyh i vtorichnyh reakcijah soprovozhdajushhih jadernye prevrashhenija. Pri obsuzhdenii roli vtorogo komponenta uchityvajutsja otlichija preobladajushhih mehanizmov ego reakcij v razlichnyh koncentracionnyh intervalah. Rassmatrivajutsja v chastnosti vozmozhnost' mezhmolekuljarnoj peredachi jenergii radiacionnoj zashhity, a takzhe mehanizmy sootvetstvujushhih processov. (author)

  8. Genetic Screens in Yeast to Identify BRCA1 Modifiers

    National Research Council Canada - National Science Library

    Plon, Sharon E

    2004-01-01

    .... The yeast RAD9 protein has similar functions and sequence motifs as BRCA1 and we proposed to identify candidate modifier loci by identifying haploinsufficient mutations at a second locus that alters...

  9. Stage-specific effects of X-irradiation on Yeast meiosis

    International Nuclear Information System (INIS)

    Thorne, L.W.; Byers, B.

    1993-01-01

    Previous work has shown that cdc 13 causes meiotic arrest of Saccharomyces cerevisiae following DNA replication by a RAD9-dependent mechanism. In the present work, the authors have further investigated the implicit effects of chromosomal lesions on progression through meiosis by exposing yeast cells to X-irradiation at various times during sporulation. They find that exposure of RAD9 cells to X-irradiation early in meiosis prevents sporulation, arresting the cells at a stage prior to premeiotic DNA replication. rad9 meiotic cells are much less responsive to X-irradiation damage, completing sporulation after treatment with doses sufficient to cause arrest of RAD9 strains. These findings thereby reveal a RAD9-dependent checkpoint function in meiosis that is distinct from the G 2 arrest previously shown to result from cdc 13 dysfunction. Analysis of the spores that continued to be produced by either RAD9 or rad9 cultures that were X-irradiated in later stages of sporulation revealed most spores to be viable, even after exposure to radiation doses sufficient to kill most vegetative cells. This finding demonstrates that the lesions induced by X-irradiation at later times fail to trigger the checkpoint function revealed by cdc 13 arrest and suggests that the lesions may be subject to repair by serving as intermediates in the recombination process. Strains mutant for chromosomal synapsis and recombination, and therefore defective in meiotic disjunction, were tested for evidence that X-ray-induced lesions might alleviate inviability by promoting recombination. Enhancement of spore viability when spo 11 (but not hop 1) diploids were X-irradiated during meiosis indicates that induced lesions may partially substitute for SPO 11-dependent functions that are required for the initiation of recombination. 74 refs., 3 figs., 6 tabs

  10. CDC28, NETI, and HFII are required for checkpoints in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Koltovaya, N.A.; Kadyshevskaya, E.Yu.; Roshina, M.P.; Devin, A.B.

    2009-01-01

    The involvement of SRM genes selected as genes affecting genetic stability and radiosensitivity in a cell cycle arrest under the action of damaging agents was studied. It was shown that the srm5/cdc28-srm, srm8/netI-srm, and srmI2/hfiI-srm mutations prevent checkpoint activation by DNA damage, particularly the G 0 /S (srm5, srm8), G 1 /S (srm5, srm8, srm12), S (srm8, srm12) and S/G 2 (srm5) checkpoints. It seems that in budding yeast the CDC28, HFII/ADAI, and NETI genes mediate cellular response induced by DNA damage with checkpoint control. The well-known checkpoint-genes RAD9, RAD17, RAD24, and RAD53, and the genes CDC28, and NETI have been found to belong to one epistasis group named RAD9-group as regards cell sensitivity to γ radiation. An analysis of the radiosensitivity of double mutants has revealed that the mutation cdc-28-srm is hypostatic to each of mutations rad9Δ, and rad24Δ, and additive to rad17Δ. The mutation netI-srm is hypostatic to the mutations rad9Δ but additive to rad17Δ, rad24Δ, and rad53. The mutation hfiI-srm has an additive effect in compound with the mutations rad24Δ and rad9Δ. So, investigations of epistatic interactions have demonstrated a branched RAD9-dependent pathway. The analyzed genes can also participate in a minor mechanism involved in determining cell radiation sensitivity independently of the mentioned RAD9-dependent pathway

  11. Phosphorylation of the Budding Yeast 9-1-1 Complex Is Required for Dpb11 Function in the Full Activation of the UV-Induced DNA Damage Checkpoint▿ †

    Science.gov (United States)

    Puddu, Fabio; Granata, Magda; Di Nola, Lisa; Balestrini, Alessia; Piergiovanni, Gabriele; Lazzaro, Federico; Giannattasio, Michele; Plevani, Paolo; Muzi-Falconi, Marco

    2008-01-01

    Following genotoxic insults, eukaryotic cells trigger a signal transduction cascade known as the DNA damage checkpoint response, which involves the loading onto DNA of an apical kinase and several downstream factors. Chromatin modifications play an important role in recruiting checkpoint proteins. In budding yeast, methylated H3-K79 is bound by the checkpoint factor Rad9. Loss of Dot1 prevents H3-K79 methylation, leading to a checkpoint defect in the G1 phase of the cell cycle and to a reduction of checkpoint activation in mitosis, suggesting that another pathway contributes to Rad9 recruitment in M phase. We found that the replication factor Dpb11 is the keystone of this second pathway. dot1Δ dpb11-1 mutant cells are sensitive to UV or Zeocin treatment and cannot activate Rad53 if irradiated in M phase. Our data suggest that Dpb11 is held in proximity to damaged DNA through an interaction with the phosphorylated 9-1-1 complex, leading to Mec1-dependent phosphorylation of Rad9. Dpb11 is also phosphorylated after DNA damage, and this modification is lost in a nonphosphorylatable ddc1-T602A mutant. Finally, we show that, in vivo, Dpb11 cooperates with Dot1 in promoting Rad9 phosphorylation but also contributes to the full activation of Mec1 kinase. PMID:18541674

  12. Production and characterization of radiation-sensitive meiotic mutants of Coprinus cinereus

    International Nuclear Information System (INIS)

    Zolan, M.E.; Tremel, C.J.; Pukkila, P.J.

    1988-01-01

    We have isolated four gamma-sensitive mutants of the basidiomycete Coprinus cinereus. When homozygous, two of these (rad 3-1 and rad 9-1) produce fruiting bodies with very few viable basidiospores, the products of meiosis in this organism. A less radiation-sensitive allele of RAD 3, rad 3-2, causes no apparent meiotic defect in homozygous strains. Quantitative measurements of oidial survival of rad 3-1;rad 9-1 double mutants compared to the single mutants indicated that rad 3-1 and rad 9-1 mutants are defective in the same DNA repair pathway. In the pew viable basidiospores that are produced by these two strains, essentially normal levels of meiotic recombination can be detected. None of the mutants exhibits increased sensitivity to UV radiation. Cytological examination of meiotic chromosomes from mutant and wild-type fruiting bodies showed that rad 3-1 homozygous strains fail to condense and pair homologous chromosomes during prophase I. Although rad 9-1 strains are successful at chromosome pairing, meiosis is usually not completed in these mutants

  13. Human genetic marker for resistance to radiations and chemicals. 1998 annual progress report

    International Nuclear Information System (INIS)

    Lieberman, H.B.

    1998-01-01

    'The broad objective of the project is to understand the molecular basis for the response of cells to radiations and chemicals, with the pragmatic goal of being able to identify human subpopulations that are exceptionally sensitive to DNA damaging agents. The project focuses on HRAD9, a human orthologue of the fission yeast Schizosaccharomyces pombe gene rad9. S. pombe rad9::ura4+ mutant cells are highly sensitive to ionizing radiation, UV and many chemicals, such as the DNA synthesis inhibitor hydroxyurea. They also lack the ability to delay cycling transiently in S phase or in G2 following a block in DNA replication or after incurring DNA damage, respectively -i.e., they lack checkpoint controls. The attempt by mutant cells to progress through mitosis in the absence of fully intact DNA accounts at least in part for their sensitivity to DNA damaging agents. Cells bearing rad9::ura4+ also aberrantly regulate UVDE, an enzyme that participates in a secondary DNA excision repair pathway. The key role played by S. pombe rad9 in promoting resistance to chemicals and radiations suggests that the evolutionarily conserved human cognate also has important functions in mammals. The first set of aims in this proposal centers on characterizing the structure and expression of HRAD9, to assess structure/function relationships and potentially link protein activity to a specific tissue. The next set of aims focuses on determining the role of HRAD9 in radio/chemoresponsiveness and cancer.'

  14. Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.

    Directory of Open Access Journals (Sweden)

    Nan Li

    Full Text Available Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG. In this study we used mouse embryonic stem (MES and mouse embryonic fibroblast (MEF cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS. Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR defects.

  15. Cellular radiation effects and hyperthermia cell cycle kinetics of radiation sensitive mutants of saccharomyces cerevisiae after x-irradiation and hyperthermia

    International Nuclear Information System (INIS)

    Fingerhut, R.; Kiefer, J.; Otto, F.

    1983-01-01

    Radiosensitive mutants rad2, rad9, and rad51 of Saccharomyces cerevisiae were X-irradiated with 120 Gy or 60 Gy, heated at 50 0 C for 30 min or treated with a combination of both and incubated in nutrient medium at 30 0 C. Cell number, percentage of budding cells, and cell cycle progression were determined in 45-min intervals. Cell cycle kinetics were investigated by flow cytofluorometry. Hyperthermia leads mainly to a lengthening of G1, whereas X-rays arrest cells of the rad2 and rad9 mutant in G2 and the rad51 - mutant additionaly in a state with DNA contents above G2. Cell division dealy is influenced by oxygen in all strains but to a lesser extent in the rad2 mutant. The effect of the combined treatment appears to be merely additive in the rad2 and rad9 mutant while the rad51 mutant is sensitized to X-irradiation by hyperthermia. No selective action of hyperthermia on hypoxic cells was found. (orig.)

  16. Lack of chemically induced mutation in repair-deficient mutants of yeast

    International Nuclear Information System (INIS)

    Prakash, L.

    1974-01-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), β-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents. (auth)

  17. Lack of chemically induced mutation in repair-deficient mutants of yeast.

    Science.gov (United States)

    Prakash, L

    1974-12-01

    Two genes, rad6 and rad9, that confer radiation sensitivity in the yeast Saccharomyces cerevisiae also greatly reduce the frequency of chemically-induced reversions of a tester mutant cyc1-131, which is a chain initiation mutant in the structural gene determining iso-1-cytochrome c. Mutations induced by ethyl methanesulfonate (EMS), diethyl sulfate (DES), methyl methanesulfonate (MMS), dimethyl sulfate (DMS), nitroquinoline oxide (NQO), nitrosoguanidine (NTG), nitrogen mustard (HN2), beta-propiolactone, and tritiated uridine, as well as mutations induced by ultraviolet light (UV) and ionizing radiation were greatly diminished in strains homozygous for either the rad6 or rad9 gene. Nitrous acid and nitrosoimidazolidone (NIL), on the other hand, were highly mutagenic in these repair-deficient mutants, and at low doses, these mutagens acted with about the same efficiency as in the normal RAD strain. At high doses of either nitrous acid or NIL, however, reversion frequencies were significantly reduced in the two rad mutants compared to normal strains. Although both rad mutants are immutable to about the same extent, the rad9 strains tend to be less sensitive to the lethal effect of chemical mutagens than rad6 strains. It is concluded that yeast requires a functional repair system for mutation induction by chemical agents.

  18. Effects of γ-radiation on cell growth, cell cycle and promoter methylation of 22 cell cycle genes in the 1321NI astrocytoma cell line.

    Science.gov (United States)

    Alghamian, Yaman; Abou Alchamat, Ghalia; Murad, Hossam; Madania, Ammar

    2017-09-01

    DNA damage caused by radiation initiates biological responses affecting cell fate. DNA methylation regulates gene expression and modulates DNA damage pathways. Alterations in the methylation profiles of cell cycle regulating genes may control cell response to radiation. In this study we investigated the effect of ionizing radiation on the methylation levels of 22 cell cycle regulating genes in correlation with gene expression in 1321NI astrocytoma cell line. 1321NI cells were irradiated with 2, 5 or 10Gy doses then analyzed after 24, 48 and 72h for cell viability using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliu bromide) assay. Flow cytometry were used to study the effect of 10Gy irradiation on cell cycle. EpiTect Methyl II PCR Array was used to identify differentially methylated genes in irradiated cells. Changes in gene expression was determined by qPCR. Azacytidine treatment was used to determine whether DNA methylation affectes gene expression. Our results showed that irradiation decreased cell viability and caused cell cycle arrest at G2/M. Out of 22 genes tested, only CCNF and RAD9A showed some increase in DNA methylation (3.59% and 3.62%, respectively) after 10Gy irradiation, and this increase coincided with downregulation of both genes (by 4 and 2 fold, respectively). with azacytidine confirmed that expression of CCNF and RAD9A genes was regulated by methylation. 1321NI cell line is highly radioresistant and that irradiation of these cells with a 10Gy dose increases DNA methylation of CCNF and RAD9A genes. This dose down-regulates these genes, favoring G2/M arrest. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  19. ATM signaling and 53BP1

    International Nuclear Information System (INIS)

    Zgheib, Omar; Huyen, Yentram; DiTullio, Richard A.; Snyder, Andrew; Venere, Monica; Stavridi, Elena S.; Halazonetis, Thanos D.

    2005-01-01

    The ATM (mutated in Ataxia-Telangiectasia) protein kinase is an important player in signaling the presence of DNA double strand breaks (DSBs) in higher eukaryotes. Recent studies suggest that ATM monitors the presence of DNA DSBs indirectly, through DNA DSB-induced changes in chromatin structure. One of the proteins that sense these chromatin structure changes is 53BP1, a DNA damage checkpoint protein conserved in all eukaryotes and the putative ortholog of the S. cerevisiae RAD9 protein. We review here the mechanisms by which ATM is activated in response to DNA DSBs, as well as key ATM substrates that control cell cycle progression, apoptosis and DNA repair

  20. Prediction of radiotherapy induced normal tissue adverse reactions: the role of double-strand break repair

    International Nuclear Information System (INIS)

    Rao, B.S. Satish; Mumbrekar, K.D.; Goutham, H.V.; Donald, J.F.; Vadhiraja, M.B.; Satyamoorthy, K.

    2016-01-01

    We aimed at evaluating the predictive potential of DSB repair kinetics (using γH2AX foci assay) in lymphocytes and analysed the genetic variants in the selected radioresponsive candidate genes like XRCC3, LIG4, NBN, CD44, RAD9A, LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 on the individual susceptibility to radiotherapy (RT) induced acute skin reactions among the head and neck cancer (HNC), and breast cancer (BC) patients. All the 183 HNC and 132 BC patients were treated by a 3-dimensional conformal RT technique

  1. Effect of genes controlling radiation sensitivity on chemically induced mutations in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Prakash, L.

    1976-01-01

    The effect of 16 different genes (rad) conferring radiation sensitivity on chemically induced reversion in the yeast Saccharomyces cerevisiae was determined. The site of reversion used was a well-defined chain initiation mutant mapping in the structural gene coding for iso-1-cytochrome c. High doses of EMS and HNO 2 resulted in decreased reversion of cyc1-131 in rad6, rad9 and rad15 strains compared to the normal RAD + strains. In addition, rad52 greatly decreased EMS reversion of cyc1-131 but had no effect on HNO 2 -induced reversion; rad18, on the other hand, increased HNO 2 -induced reversion but did not alter EMS-induced reversion. When NQO was used as the mutagen, every rad gene tested, except for rad18, had an effect on reversion; rad6, rad9, rad15, rad17, rad18, rad22, rev1, rev2, and rev3 lowered NQO reversion while rad1, rad2, rad3, rad4, rad10, rad12, and rad16 increased it compared to the RAD + strain. The effect of rad genes on chemical mutagenesis is discussed in terms of their effect on uv mutagenesis. It is concluded that although the nature of the repair pathways may differ for uv- and chemically-induced mutations in yeast, a functional repair system is required for the induction of mutation by the chemical agents NQO, EMS, and HNO 2

  2. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

    Science.gov (United States)

    Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

    2015-05-12

    Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

  3. An origin-deficient yeast artificial chromosome triggers a cell cycle checkpoint.

    Science.gov (United States)

    van Brabant, A J; Buchanan, C D; Charboneau, E; Fangman, W L; Brewer, B J

    2001-04-01

    Checkpoint controls coordinate entry into mitosis with the completion of DNA replication. Depletion of nucleotide precursors by treatment with the drug hydroxyurea triggers such a checkpoint response. However, it is not clear whether the signal for this hydroxyurea-induced checkpoint pathway is the presence of unreplicated DNA, or rather the persistence of single-stranded or damaged DNA. In a yeast artificial chromosome (YAC) we have engineered an approximately 170 kb region lacking efficient replication origins that allows us to explore the specific effects of unreplicated DNA on cell cycle progression. Replication of this YAC extends the length of S phase and causes cells to engage an S/M checkpoint. In the absence of Rad9 the YAC becomes unstable, undergoing deletions within the origin-free region.

  4. Systematic Analysis of the DNA Damage Response Network in Telomere Defective Budding Yeast

    Directory of Open Access Journals (Sweden)

    Eva-Maria Holstein

    2017-07-01

    Full Text Available Functional telomeres are critically important to eukaryotic genetic stability. Scores of proteins and pathways are known to affect telomere function. Here, we report a series of related genome-wide genetic interaction screens performed on budding yeast cells with acute or chronic telomere defects. Genetic interactions were examined in cells defective in Cdc13 and Stn1, affecting two components of CST, a single stranded DNA (ssDNA binding complex that binds telomeric DNA. For comparison, genetic interactions were also examined in cells with defects in Rfa3, affecting the major ssDNA binding protein, RPA, which has overlapping functions with CST at telomeres. In more complex experiments, genetic interactions were measured in cells lacking EXO1 or RAD9, affecting different aspects of the DNA damage response, and containing a cdc13-1 induced telomere defect. Comparing fitness profiles across these data sets helps build a picture of the specific responses to different types of dysfunctional telomeres. The experiments show that each context reveals different genetic interactions, consistent with the idea that each genetic defect causes distinct molecular defects. To help others engage with the large volumes of data, the data are made available via two interactive web-based tools: Profilyzer and DIXY. One particularly striking genetic interaction observed was that the chk1∆ mutation improved fitness of cdc13-1 exo1∆ cells more than other checkpoint mutations (ddc1∆, rad9∆, rad17∆, and rad24∆, whereas, in cdc13-1 cells, the effects of all checkpoint mutations were similar. We show that this can be explained by Chk1 stimulating resection—a new function for Chk1 in the eukaryotic DNA damage response network.

  5. Sila kojom vazduh pritiska pokretnu ploču/Force of the air pressure on a moving plate

    Directory of Open Access Journals (Sweden)

    Leonid Ivanovich Gretchihin

    2014-10-01

    Full Text Available U radu je razrađena matematički model gasodinamičkog opstrujavanja ravne ploče pri njenom kretanju sa pozitivnim i negativnim napadnim uglom. Pokazano je da pri malim brzinama kretanja, silu uzgona i čeoni otpor određuje gasodinamički tok vazduha u izlaznoj oblasti opstrujavanja, a pri brzinama kretanja koje su bliske brzini zvuka odlučujuću ulogu vrši uzajamno udarno dejstvo ploče sa molekulima okružujuće sredine u ulaznoj oblasti opstrujavanja. Otcepljena struja iza ploče se ne pojavljuje pri malim brzinama kretanja. Određeni su uslovi kada čeoni otpor i sila uzgona ploče menjaju znak. / (ruski Razrabotana matematičeskaja model' gazodinamičeskogo obtekanija ploskoj plastiny pri ee dviženii s položitel'nym i otricatel'nym uglom ataki. Pokazano, čto pri malyh skorostjah dviženija plastiny pod''emnaja sila i lobovoe soprotivlenie opredeljajutsja gazodinamikoj tečenija vozduha v tyl'noj oblasti, a pri skorostjah dviženija blizkih k skorosti zvuka rešajuščuju rol' vypolnjaet udarnoe vzaimodejstvie plastiny s molekulami okružajuščej sredy v perednej oblasti. Sryvnoe tečenie za plastinoj pri malyh skorostjah dviženija ne voznikaet. Opredeleny uslovija, kogda lobovoe soprotivlenie i pod''emnaja sila plastiny izmenjaet znak. / This paper developed a mathematical model of gas dynamic fluid flow for a flat plate during its movement with positive and negative angles of attack. It is shown that at low velocities, the lifting force and the frontal resistance are determined by gasdynamic air flow in the fluid flow exit areawhile at velocities close to the speed of sound the decisive role is played by a mutualeffect of the pplate coliding with molecules of the surrounding environment in the fluid flow incidence field. The airflow behind the plate does not appear at low velocities. The conditions when the frontal resistance and the lifting force change the sign are determined.

  6. Role of the Checkpoint Clamp in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  7. Viral interference with DNA repair by targeting of the single-stranded DNA binding protein RPA.

    Science.gov (United States)

    Banerjee, Pubali; DeJesus, Rowena; Gjoerup, Ole; Schaffhausen, Brian S

    2013-10-01

    Correct repair of damaged DNA is critical for genomic integrity. Deficiencies in DNA repair are linked with human cancer. Here we report a novel mechanism by which a virus manipulates DNA damage responses. Infection with murine polyomavirus sensitizes cells to DNA damage by UV and etoposide. Polyomavirus large T antigen (LT) alone is sufficient to sensitize cells 100 fold to UV and other kinds of DNA damage. This results in activated stress responses and apoptosis. Genetic analysis shows that LT sensitizes via the binding of its origin-binding domain (OBD) to the single-stranded DNA binding protein replication protein A (RPA). Overexpression of RPA protects cells expressing OBD from damage, and knockdown of RPA mimics the LT phenotype. LT prevents recruitment of RPA to nuclear foci after DNA damage. This leads to failure to recruit repair proteins such as Rad51 or Rad9, explaining why LT prevents repair of double strand DNA breaks by homologous recombination. A targeted intervention directed at RPA based on this viral mechanism could be useful in circumventing the resistance of cancer cells to therapy.

  8. Biological effects and repair of damage photoinduced by a derivative of psoralen substituted at the 3,4 reaction site

    International Nuclear Information System (INIS)

    Averbeck, D.; Moustacchi, E.; Bisagni, E.

    1978-01-01

    A newly-synthesized linear psoralen derivative, 3-carbethoxypsoralen is shown to bind to yeast nucleic acids after 365-nm light treatment. As compared to 8-methoxypsoralen, a well-known bifunctional furocoumarin, 3-carbethoxypsoralen exhibits a high photoaffinity for DNA in vivo. Both compounds bind and photoreact more efficiently in vivo than in vitro. In contrast to 8-methoxypsoralen, 3-carbethoxypsoralen does not form cross-links in yeast DNA as demonstrated by heat denaturation-reassociation studies at least in the ranges of doses used. Thus 3-carbethoxypsoralen reacts as a monofunctional compound. Wild-type cells of Saccharomyces cerevisiae are 6 times more resistant to 3-carbethoxypsoralen than to 8-methoxypsoralen plus 365 nm light treatment in terms of lethal effect. In comparison to angelicin, another monofunctional (but angular) furocoumarin, 3-carbethoxypsoralen is more photoreactive. When the photoaffinity for DNA of 8-methoxypsoralen and 3-carbethoxypsoralen are considered in relation to photoinduced cell killing, it is clear that monoadducts are very efficiently repaired in wild-type cells. In contrast to the additivity obtained with 8-methoxypsoralen, a synergistic interaction of the two different repair pathways blocked by the rad 2 and the rad 9 mutation is observed after 3-carbethoxypsoralen plus 365 nm light. Dark holding experiments show that the excision repair function which is present in wild-type and radsub(9-4) cells is important for dark recovery. (Auth.)

  9. Inhibition of ribosomal RNA synthesis in yeast by ionizing radiations

    Energy Technology Data Exchange (ETDEWEB)

    Weber, K; Kiefer, J [Giessen Univ. (Germany, F.R.). Strahlenzentrum

    1984-12-01

    Synthesis of ribosomal RNA(r-RNA) was measured for 1 h after exposure of Saccharomyces cerevisiae to ..gamma..-rays, X-rays or ..cap alpha.. particles. ..gamma..- or X-ray induced transcription inhibition was always found to decrease exponentially with dose. D/sub 0/ values of 2150 or 1950 Gy were determined in wild-type cells, corresponding to a mean energy of about 60 eV per r-RNA gene. The finding of differential sensitivities of the two high molecular-weight r-RNA species which are cotranscribed from r-DNA is compatible with the existence of a transcription terminating mechanism. Cells from a mutant strain (rad-9), radiation sensitive to colony forming ability, showed an approximately equal sensitivity for transcription inhibition compared to the wild-type (D/sub 0/ (2095) = 2400 Gy). Inactivation of r-RNA synthesis in cells exposed to ..cap alpha..-particles at room-temperature showed a decreased sensitivity with higher particle fluences ('resistant tail'). This phenomenon was drastically reduced if the temperature during irradiation was lowered to 4/sup 0/C and completely abolished when dried cells were used. An inactivation cross-section for ..cap alpha..-particle induced transcription inhibition of about 0.02 ..mu..m/sup 2/ can be derived from the experimental data.

  10. The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway

    International Nuclear Information System (INIS)

    Cohen-Fix, O.; Koshland, D.

    1997-01-01

    Inhibition of DNA replication and physical DNA damage induce checkpoint responses that arrest cell cycle progression at two different stages. In Saccharomyces cerevisiae, the execution of both checkpoint responses requires the Mec1 and Rad53 proteins. This observation led to the suggestion that these checkpoint responses are mediated through a common signal transduction pathway. However, because the checkpoint-induced arrests occur at different cell cycle stages, the downstream effectors mediating these arrests are likely to be distinct. We have previously shown that the S. cerevisiae protein Pds1p is an anaphase inhibitor and is essential for cell cycle arrest in mitosis in the presence DNA damage. Herein we show that DNA damage, but not inhibition of DNA replication, induces the phosphorylation of Pds1p. Analyses of Pds1p phosphorylation in different checkpoint mutants reveal that in the presence of DNA damage, Pds1p is phosphorylated in a Mec1p- and Rad9p-dependent hut Rad53p-independent manner. Our data place Pds1p and Rad53p on parallel branches of the DNA damage checkpoint pathway. We suggest that Pds1p is a downstream target of the DNA damage checkpoint pathway and that it is involved in implementing the DNA damage checkpoint arrest specifically in mitosis

  11. Lysine residue 185 of Rad1 is a topological but not a functional counterpart of lysine residue 164 of PCNA.

    Directory of Open Access Journals (Sweden)

    Niek Wit

    Full Text Available Monoubiquitylation of the homotrimeric DNA sliding clamp PCNA at lysine residue 164 (PCNA(K164 is a highly conserved, DNA damage-inducible process that is mediated by the E2/E3 complex Rad6/Rad18. This ubiquitylation event recruits translesion synthesis (TLS polymerases capable of replicating across damaged DNA templates. Besides PCNA, the Rad6/Rad18 complex was recently shown in yeast to ubiquitylate also 9-1-1, a heterotrimeric DNA sliding clamp composed of Rad9, Rad1, and Hus1 in a DNA damage-inducible manner. Based on the highly similar crystal structures of PCNA and 9-1-1, K185 of Rad1 (Rad1(K185 was identified as the only topological equivalent of PCNA(K164. To investigate a potential role of posttranslational modifications of Rad1(K185 in DNA damage management, we here generated a mouse model with a conditional deletable Rad1(K185R allele. The Rad1(K185 residue was found to be dispensable for Chk1 activation, DNA damage survival, and class switch recombination of immunoglobulin genes as well as recruitment of TLS polymerases during somatic hypermutation of immunoglobulin genes. Our data indicate that Rad1(K185 is not a functional counterpart of PCNA(K164.

  12. Loss of yeast peroxiredoxin Tsa1p induces genome instability through activation of the DNA damage checkpoint and elevation of dNTP levels.

    Directory of Open Access Journals (Sweden)

    Hei-Man Vincent Tang

    2009-10-01

    Full Text Available Peroxiredoxins are a family of antioxidant enzymes critically involved in cellular defense and signaling. Particularly, yeast peroxiredoxin Tsa1p is thought to play a role in the maintenance of genome integrity, but the underlying mechanism is not understood. In this study, we took a genetic approach to investigate the cause of genome instability in tsa1Delta cells. Strong genetic interactions of TSA1 with DNA damage checkpoint components DUN1, SML1, and CRT1 were found when mutant cells were analyzed for either sensitivity to DNA damage or rate of spontaneous base substitutions. An elevation in intracellular dNTP production was observed in tsa1Delta cells. This was associated with constitutive activation of the DNA damage checkpoint as indicated by phosphorylation of Rad9/Rad53p, reduced steady-state amount of Sml1p, and induction of RNR and HUG1 genes. In addition, defects in the DNA damage checkpoint did not modulate intracellular level of reactive oxygen species, but suppressed the mutator phenotype of tsa1Delta cells. On the contrary, overexpression of RNR1 exacerbated this phenotype by increasing dNTP levels. Taken together, our findings uncover a new role of TSA1 in preventing the overproduction of dNTPs, which is a root cause of genome instability.

  13. Molecular Signatures in the Prevention of Radiation Damage by the Synergistic Effect of N-Acetyl Cysteine and Qingre Liyan Decoction, a Traditional Chinese Medicine, Using a 3-Dimensional Cell Culture Model of Oral Mucositis

    Directory of Open Access Journals (Sweden)

    Maria P. Lambros

    2015-01-01

    Full Text Available Qingre Liyan decoction (QYD, a Traditional Chinese medicine, and N-acetyl cysteine (NAC have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1, protective genes (EGFR and PPARD, and genes of the NFκB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs. NAC-QYD treatment involves the protective effect of Nrf2, NFκB, and DNA repair factors.

  14. Individual Genetic Susceptibility

    International Nuclear Information System (INIS)

    Hall, Eric J.

    2008-01-01

    Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimental radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 and Brca1. The purpose of radiation protection is to prevent deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: (a) Ocular cataracts as an important and relevant deterministic effect, and (b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.

  15. Genetic analysis of γ-ray mutagenesis in yeast. Vol. 3

    International Nuclear Information System (INIS)

    McKee, R.H.; Lawrence, C.W.

    1980-01-01

    Comparisons between the 60 Co γ-ray survival curves of diploid strains of the yeast Saccharomyces cerevisiae that are homozygous for two non-allelic radiation-sensitive mutations and the corresponding single-mutant diploids suggest that there are two main types of repair of ionizing radiation damage in this organism. The first, which is defined by the rad52 epistasis group, depends on the activities of the RAD50 through RAD57 genes and is responsible for repairing the larger amount of lethal damage. Previous work [22] shows that this type of repair is essentially error-free. The second, defined by the rad6 epistasis group, depends on the activities of the RAD6, RAD9, RAD18, REV1 and REV3 genes and repairs a smaller, though still substantial, amount of lethal damage. It is also responsible for induced mutagenesis [22,23]. Data for survival and mutation induction after irradiation in air and partial anoxia show that oxygen-dependent damage can be repaired by either of these two pathways. They also show similar oxygen-enhancement ratios for survival and mutagenesis. (orig.)

  16. The tumor suppressor homolog in fission yeast, myh1+, displays a strong interaction with the checkpoint gene rad1+

    International Nuclear Information System (INIS)

    Jansson, Kristina; Warringer, Jonas; Farewell, Anne; Park, Han-Oh; Hoe, Kwang-Lae; Kim, Dong-Uk; Hayles, Jacqueline; Sunnerhagen, Per

    2008-01-01

    The DNA glycosylase MutY is strongly conserved in evolution, and homologs are found in most eukaryotes and prokaryotes examined. This protein is implicated in repair of oxidative DNA damage, in particular adenine mispaired opposite 7,8-dihydro-8-oxoguanine. Previous investigations in Escherichia coli, fission yeast, and mammalian cells show an association of mutations in MutY homologs with a mutator phenotype and carcinogenesis. Eukaryotic MutY homologs physically associate with several proteins with a role in replication, DNA repair, and checkpoint signaling, specifically the trimeric 9-1-1 complex. In a genetic investigation of the fission yeast MutY homolog, myh1 + , we show that the myh1 mutation confers a moderately increased UV sensitivity alone and in combination with mutations in several DNA repair genes. The myh1 rad1, and to a lesser degree myh1 rad9, double mutants display a synthetic interaction resulting in enhanced sensitivity to DNA damaging agents and hydroxyurea. UV irradiation of myh1 rad1 double mutants results in severe chromosome segregation defects and visible DNA fragmentation, and a failure to activate the checkpoint. Additionally, myh1 rad1 double mutants exhibit morphological defects in the absence of DNA damaging agents. We also found a moderate suppression of the slow growth and UV sensitivity of rhp51 mutants by the myh1 mutation. Our results implicate fission yeast Myh1 in repair of a wider range of DNA damage than previously thought, and functionally link it to the checkpoint pathway

  17. Relative accuracy of the BD Logic and FreeStyle blood glucose meters.

    Science.gov (United States)

    2007-04-01

    The BD Logic((R)) (Becton, Dickinson and Co., Franklin Lakes, NJ) and FreeStyle((R)) (Abbott Diabetes Care, Alameda, CA) meters are used to transmit data directly to insulin pumps for calculation of insulin doses and to calibrate continuous glucose sensors as well as to monitor blood glucose levels. The accuracy of the two meters was evaluated in two inpatient studies conducted by the Diabetes Research in Children Network (DirecNet). In both studies, meter glucose measurements made with either venous or capillary blood were compared with reference glucose measurements made by the DirecNet Central Laboratory at the University of Minnesota using a hexokinase enzymatic method. The BD Logic tended to read lower than the laboratory reference regardless of whether venous (median difference = -9 mg/dL) or capillary blood (median difference = -7 mg/dL) was used. This resulted in lower accuracy of the BD Logic compared with the FreeStyle meter based on the median relative absolute difference (RAD) for both venous blood (median RAD, 9% vs. 5%, P blood (median RAD, 11% vs. 6%, P = 0.008). The greatest discrepancy in the performance of the two meters was at higher reference glucose values. Accuracy was not significantly different when the reference was < or = 70 mg/dL. The BD Logic meter is less accurate than the FreeStyle meter.

  18. Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination

    DEFF Research Database (Denmark)

    Germann, Susanne Manuela; Østergaard, Vibe Hallundbæk; Haas, Caroline

    2011-01-01

    DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its...... and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-function mutant, dpb11-PF, that is sensitive to DSB-inducing agents yet remains proficient for DNA replication and the S-phase checkpoint at the permissive temperature. The dpb11-PF mutant...... homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1...

  19. Temperature-sensitive defects of the GSP1gene, yeast Ran homologue, activate the Tel1-dependent pathway

    International Nuclear Information System (INIS)

    Hayashi, Naoyuki; Murakami, Seishi; Tsurusaki, Susumu; Nagaura, Zen-ichiro; Oki, Masaya; Nishitani, Hideo; Kobayashi, Masahiko; Shimizu, Hiroko; Yamamoto, Ken-ichi; Nishimoto, Takeharu

    2007-01-01

    RanGTPase is involved in many cellular processes. It functions in nuclear-cytosolic transport and centrosome formation. Ran also localizes to chromatin as RCC1 does, its guanine nucleotide exchange factor, but Ran's function on chromatin is not known. We found that gsp1, a temperature-sensitive mutant of GSP1, a Saccharomyces cerevisiae Ran homologue, suppressed the hydroxyurea (HU) and ultra violet (UV) sensitivities of the mec1 mutant. In UV-irradiated mec1 gsp1 cells, Rad53 was phosphorylated despite the lack of Mec1. This suppression depended on the TEL1 gene, given that the triple mutant, mec1 gsp1 tel1, was unable to grow. The gsp1 mutations also suppressed the HU sensitivity of the rad9 mutant in a Tel1-dependent manner, but not the HU sensitivity of the rad53 mutant. These results indicated that Rad53 was activated by the Tel1 pathway in mec1 gsp1 cells, suggesting that Gsp1 helps regulate the role switching the ATM family kinases Mec1 and Tel1

  20. The Possibility of Making a Quantitative Study of the Precipitin Reaction by Gamma-Radioactive Tracers; Possibilite d'une Etude Quantitative de la Reaction de Precipitation par Marquage a l'Aide d'Emetteurs Gamma; Vozmozhnost' kolichestvennogo opredeleniya reaktsii osazhdeniya s pomoshch'yu gamma-radioaktivnykh indikatorov; Estudio Cuantitativo de la Reaccion de Precipitacion con Ayuda de Indicadores Gamma

    Energy Technology Data Exchange (ETDEWEB)

    Bonev, L.; Todorov, S.; Robev, S. [Nauchno-Issledovatel' skij Institut Radiologii i Radiacionnoj Bezopasnosti, Sofija (Bulgaria)

    1965-10-15

    indicadores gamma que no reaccionan quimicamente con las moleculas de albumina. Como indicadores pueden utilizarse ciertos compuestos de cromo, manganeso y hierro que, por su teridencia a hidrolizarse, permiten fijar el indicador radiactivo en el antigeno y en el anticuerpo, respectivamente. La radiactividad de los componentes se determino con ayuda de un analizador multicanal de amplitud de impulsos. Los resultados obtenidos demuestran que la curva de precipitacion, trazada sobre la base de los datos radiometricos, concuerda con la que se obtiene por los metodos cuantitativos corrientemente empleados en la valoracion de la albumiRa. Los autores examinan las posibilidades de aplicacion del metodo descrito. (author) [Russian] Soobshhajutsja pervye rezul'taty kolichestvennogo opredelenija reakcii osazhdenija (obrazovanija kompleksa antigen-antitelo) posredstvom mechenija precipitacionnyh komponentov gamma-radioaktivnymi indikatorami, ne vstupajushhimi v himicheskoe vzaimodejstvie s belkovymi molekulami. V kachestve indikatorov mogut byt' ispol'zovany hromomargancevye soedinenija i soedinenija zheleza, sklonnost' kotoryh k gidrolizu obespechivaet fiksaciju radioaktivnogo indikatora na antigene sootvetstvenno i na antitelo. Opredelenie radioaktivnosti komponentov proizvoditsja posredstvom mnogokanal'nogo amplitudnogo analizatora. Poluchennye rezul'taty pokazyvajut, chto precipitacionnaja krivaja, postroennaja na osnovanii radiometrichnyh dannyh, nahoditsja v blizkom sootvetstvii s krivoj, postroennoj izvestnymi kolichestvennymi metodami, sluzhashhimi dlja opredelenija belka. Rassmatrivajutsja vozmozhnosti primenenija jetogo metoda na praktike. (author)

  1. The Self-Correlation Function of Real Gases; Fonction d'Autocorrelation des Gaz Reels; 0424 0423 041d 041a 0426 0418 042f 0421 0410 041c 041e 041a 041e 0420 0420 0415 041b 042f 0426 0418 0418 0420 0415 0410 041b 042c 041d 042b 0425 0413 0410 0417 041e 0412 ; La Funcion de Autocorrelacion de los Gases Reales

    Energy Technology Data Exchange (ETDEWEB)

    Sigmar, D. J. [Institute for Theoretical Physics, Technical University of Vienna Vienna (Austria)

    1965-06-15

    autocorrelacion {gamma}{sub s}(K, t) para tiempos breves, incluido el primer termino no gaussiano. El desarrollo en racimo cesa despues del primer termino de interaccion, de forma que los resultados solo son validos para densidades bajas. Pero aun asi aparecen en cada coeficiente muchos tipos diferentes de racimos que contienen hasta siete puntos. En cuanto al potencial, se admite la hipotesis de un nucleo rigido formado por dos particulas. Como han demostrado Singwi y sus col., el comportamiento a largo plazo de {gamma}{sub s} viene determinado por la integral, respecto del tiempo, de la autocorrelacion de la velocidad; {integral}{sup {infinity}}{sub 0} {sub T}dt. Con el fin de determinar el integrando correspondiente a cualquier tiempo, se puede recurrir al desarrollo en racimo cuando t es pequefio, y aceptar la teoria de la difusion de Langevin en los casos en que t es grande. Se estan realizando calculos numericos. (author) [Russian] V formal'noj teorii neuprugogo rassejanija nejtronov funkcija samokorreljacii vyvedena v sredne-statisticheskih proizvodnyh vzaimodejstvie-potencial N-tela rasseivatelja. V dannom doklade jeti srednie znachenija opredeljajutsja dlja real'nyh gazov razlozheniem na gruppy, svjazannym s metodom Majera-Ursellja. Jeto privodit k polucheniju nekotoryh nelinejnyh tipov grupp, kotorye izuchajutsja v otnoshenii topologii graf, ih mnogokratnosti (metodami kombinatornogo analiza) i ih kvadratury. Kak predpolagaetsja v svjazi s problemoj mnogih tel, nekotorye iz grupp nerazdelimy, i ih neobhodimo integrirovat' s pomosh'ju schetno-reshajushhih mashin. Takim putem rasschityvaetsja funkcija samokorreljacii {gamma}{sub s}(K, t) dlja korotkih promezhutkov vremeni, v tom chisle i pervyj negaussovskij chlen. Razlozhenie na gruppy preryvaetsja posle pervogo chlena, vyrazhajushhego vzaimodejstvie, tak chto rezul'taty spravedlivy tol'ko dlja nizkoj plotnosti. Jeto tem ne menee privodit k samym razlichnym tipam grupp, v kotoryh soderzhitsja do

  2. Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer

    Science.gov (United States)

    Pussila, Marjaana; Törönen, Petri; Einarsdottir, Elisabet; Katayama, Shintaro; Krjutškov, Kaarel; Holm, Liisa; Kere, Juha; Peltomäki, Päivi; Mäkinen, Markus J; Linden, Jere; Nyström, Minna

    2018-01-01

    Abstract Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1+/−) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC. PMID:29701748

  3. The Mechanism of Nucleotide Excision Repair-Mediated UV-Induced Mutagenesis in Nonproliferating Cells

    Science.gov (United States)

    Kozmin, Stanislav G.; Jinks-Robertson, Sue

    2013-01-01

    Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such two-strand mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colony-color system was used to examine the genetic control of UV-induced mutagenesis in nondividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production of these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32, and Rad5) and in the early steps of the DNA-damage checkpoint response (Rad17, Mec3, Ddc1, Mec1, and Rad9) were required for the production of two-strand mutations. There was no involvement, however, for the Pol η translesion synthesis DNA polymerase, the Mms2-Ubc13 postreplication repair complex, downstream DNA-damage checkpoint factors (Rad53, Chk1, and Dun1), or the Exo1 exonuclease. Our data support models in which UV-induced mutagenesis in nondividing cells occurs during the Pol ζ-dependent filling of lesion-containing, NER-generated gaps. The requirement for specific DNA-damage checkpoint proteins suggests roles in recruiting and/or activating factors required to fill such gaps. PMID:23307894

  4. The KYxxL motif in Rad17 protein is essential for the interaction with the 9–1–1 complex

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Yasunori, E-mail: fukumoto@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Ikeuchi, Masayoshi; Nakayama, Yuji [Department of Biochemistry & Molecular Biology, Kyoto Pharmaceutical University, Kyoto 607-8414 (Japan); Yamaguchi, Naoto, E-mail: nyama@faculty.chiba-u.jp [Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan)

    2016-09-02

    ATR-dependent DNA damage checkpoint is the major DNA damage checkpoint against UV irradiation and DNA replication stress. The Rad17–RFC and Rad9–Rad1–Hus1 (9–1–1) complexes interact with each other to contribute to ATR signaling, however, the precise regulatory mechanism of the interaction has not been established. Here, we identified a conserved sequence motif, KYxxL, in the AAA+ domain of Rad17 protein, and demonstrated that this motif is essential for the interaction with the 9–1–1 complex. We also show that UV-induced Rad17 phosphorylation is increased in the Rad17 KYxxL mutants. These data indicate that the interaction with the 9–1–1 complex is not required for Rad17 protein to be an efficient substrate for the UV-induced phosphorylation. Our data also raise the possibility that the 9–1–1 complex plays a negative regulatory role in the Rad17 phosphorylation. We also show that the nucleotide-binding activity of Rad17 is required for its nuclear localization. - Highlights: • We have identified a conserved KYxxL motif in Rad17 protein. • The KYxxL motif is crucial for the interaction with the 9–1–1 complex. • The KYxxL motif is dispensable or inhibitory for UV-induced Rad17 phosphorylation. • Nucleotide binding of Rad17 is required for its nuclear localization.

  5. Loss of CHK1 function impedes DNA damage-induced FANCD2 monoubiquitination but normalizes the abnormal G2 arrest in Fanconi anemia.

    Science.gov (United States)

    Guervilly, Jean-Hugues; Macé-Aimé, Gaëtane; Rosselli, Filippo

    2008-03-01

    Fanconi anemia (FA) is a cancer-prone hereditary disease resulting from mutations in one of the 13 genes defining the FANC/BRCA pathway. This pathway is involved in the cellular resistance to DNA-cross-linking agents. How the FANC/BRCA pathway is activated and why its deficiency leads to the accumulation of FA cells with a 4N DNA content are still poorly answered questions. We investigated the involvement of ATR pathway members in these processes. We show here that RAD9 and RAD17 are required for DNA interstrand cross-link (ICL) resistance and for the optimal activation of FANCD2. Moreover, we demonstrate that CHK1 and its interacting partner CLASPIN that act downstream in the ATR pathway are required for both FANCD2 monoubiquitination and assembling in subnuclear foci in response to DNA damage. Paradoxically, in the absence of any genotoxic stress, CHK1 or CLASPIN depletion results in an increased basal level of FANCD2 monoubiquitination and focalization. We also demonstrate that the ICL-induced accumulation of FA cells in late S/G2 phase is dependent on ATR and CHK1. In agreement with this, CHK1 phosphorylation is enhanced in FA cells, and chemical inhibition of the ATR/CHK1 axis in FA lymphoblasts decreases their sensitivity to mitomycin C. In conclusion, this work describes a complex crosstalk between CHK1 and the FANC/BRCA pathway: CHK1 activates this pathway through FANCD2 monoubiquitination, whereas FA deficiency leads to a CHK1-dependent G2 accumulation, raising the possibility that the FANC/BRCA pathway downregulates CHK1 activation.

  6. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Pol{kappa}). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development.

  7. The tumor suppressor homolog in fission yeast, myh1{sup +}, displays a strong interaction with the checkpoint gene rad1{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Jansson, Kristina; Warringer, Jonas; Farewell, Anne [Department of Cell and Molecular Biology, Lundberg Laboratory, Goeteborg University, P.O. Box 462, Goeteborg SE-405 30 (Sweden); Park, Han-Oh [Bioneer Corporation, 49-3, Munpyeong-dong, Daedeok-gu, Daejon 306-220 (Korea, Republic of); Hoe, Kwang-Lae; Kim, Dong-Uk [Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yusong, Daejeon (Korea, Republic of); Hayles, Jacqueline [Cell Cycle Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln' s Inn Fields, London WC2A 3PX (United Kingdom); Sunnerhagen, Per [Department of Cell and Molecular Biology, Lundberg Laboratory, Goeteborg University, P.O. Box 462, Goeteborg SE-405 30 (Sweden)], E-mail: per.sunnerhagen@cmb.gu.se

    2008-09-26

    The DNA glycosylase MutY is strongly conserved in evolution, and homologs are found in most eukaryotes and prokaryotes examined. This protein is implicated in repair of oxidative DNA damage, in particular adenine mispaired opposite 7,8-dihydro-8-oxoguanine. Previous investigations in Escherichia coli, fission yeast, and mammalian cells show an association of mutations in MutY homologs with a mutator phenotype and carcinogenesis. Eukaryotic MutY homologs physically associate with several proteins with a role in replication, DNA repair, and checkpoint signaling, specifically the trimeric 9-1-1 complex. In a genetic investigation of the fission yeast MutY homolog, myh1{sup +}, we show that the myh1 mutation confers a moderately increased UV sensitivity alone and in combination with mutations in several DNA repair genes. The myh1 rad1, and to a lesser degree myh1 rad9, double mutants display a synthetic interaction resulting in enhanced sensitivity to DNA damaging agents and hydroxyurea. UV irradiation of myh1 rad1 double mutants results in severe chromosome segregation defects and visible DNA fragmentation, and a failure to activate the checkpoint. Additionally, myh1 rad1 double mutants exhibit morphological defects in the absence of DNA damaging agents. We also found a moderate suppression of the slow growth and UV sensitivity of rhp51 mutants by the myh1 mutation. Our results implicate fission yeast Myh1 in repair of a wider range of DNA damage than previously thought, and functionally link it to the checkpoint pathway.

  8. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    International Nuclear Information System (INIS)

    Kai, Mihoko; Wang, Teresa S.-F.

    2003-01-01

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Polκ). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development

  9. Lymphatic mapping and sentinel lymph node detection in patients with breast cancer

    International Nuclear Information System (INIS)

    Chen, S.L.; Du, Q.Q.; Shi, H.C.; Chen, J.X.; Wang, H.

    2002-01-01

    Objectives: To localize sentinel lymph node (SLN) and to test the hypothesis that the histologic characteristics of the SLN can predict the histologic characteristic of the remaining lymph nodes along the lymphatic chain. To calculate the absorbed dose of patients, doctors and nurses. Methods: Seventy-one patients with early-stage breast cancer underwent SLN localization using filtered technetium-99m labeled sulfur colloid, blue dye, or combination of them. SLN was identified as a blue lymph node and/or a 'hot lymph node' detected by ex vivo gamma probe. A 'hot lymph node' is the lymph node the radioactivity of which was 10 times higher than that of background. Pathological examination was performed with all resected lymph nodes. The approximate absorbed dose of the patients, doctors and nurses was calculated by using MIRD techniques. Results: For patients who were injected with only blue dye, the sensitivity, accuracy and false negative rate was 80.0%, 90.7% and 20.0% respectively. For patients who were injected with only radioactive colloids, the sensitivity, accuracy and false negative rate was 100%, 100% and 0% respectively. For patients who were injected with both blue dye and radioactive colloids, the sensitivity, accuracy and false negative rate was 100%, 100% and 100% respectively. The absorbed dose of breast tissue was 26.52 rad. The absorbed dose of nuclear medicine doctors, surgeons, nurses and pathologists was 1.9x10 -2 rad, 9.6x10 -3 rad, 3.8x10 -4 rad and 9.6x10 -3 rad respectively. Conclusions: Lymphatic mapping and SLN biopsy were the most effective when a combination of blue dye and radio-labeled sulfur colloid was used. Radio-labeled sulfur colloid was safe to patients and the medical staff. SLN biopsy had the potential value for avoiding unnecessary axillary lymph nodes resection for patients with early-stage breast cancer

  10. X-ray survival characteristics and genetic analysis for nineSaccharomyces deletion mutants that affect radiation sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Game, John C.; Williamson, Marsha S.; Baccari, Clelia

    2006-07-21

    We examine ionizing radiation (IR) sensitivity and epistasisrelationships of several Saccharomyces mutants affectingpost-translational modifications of histones H2B and H3. Mutantsbre1delta, lge1delta, and rtf1delta, defective in histone H2B lysine 123ubiquitination, show IR sensitivity equivalent to that of the dot1deltamutant that we reported on earlier, consistent with published findingsthat Dot1p requires H2B K123 ubiquitination to fully methylate histone H3K79. This implicates progressive K79 methylation rather thanmono-methylation in IR resistance. The set2delta mutant, defective in H3K36 methylation, shows mild IR sensitivity whereas mutants that abolishH3 K4 methylation resemble wild type. The dot1delta, bre1delta, andlge1delta mutants show epistasis for IR sensitivity. The paf1deltamutant, also reportedly defective in H2B K123 ubiquitination, confers nosensitivity. The rad6delta, rad51null, rad50delta, and rad9deltamutations are epistatic to bre1? and dot1delta, but rad18delta andrad5delta show additivity with bre1delta, dot1delta, and each other. Thebre1delta rad18delta double mutant resembles rad6delta in sensitivity;thus the role of Rad6p in ubiquitinating H2B accounts for its extrasensitivity compared to rad18delta. We conclude that IR resistanceconferred by BRE1 and DOT1 is mediated through homologous recombinationalrepair, not postreplication repair, and confirm findings of a G1checkpoint role for the RAD6/BRE1/DOT1 pathway.

  11. Prevention of DNA Rereplication Through a Meiotic Recombination Checkpoint Response

    Directory of Open Access Journals (Sweden)

    Nicole A. Najor

    2016-12-01

    Full Text Available In the budding yeast Saccharomyces cerevisiae, unnatural stabilization of the cyclin-dependent kinase inhibitor Sic1 during meiosis can trigger extra rounds of DNA replication. When programmed DNA double-strand breaks (DSBs are generated but not repaired due to absence of DMC1, a pathway involving the checkpoint gene RAD17 prevents this DNA rereplication. Further genetic analysis has now revealed that prevention of DNA rereplication also requires MEC1, which encodes a protein kinase that serves as a central checkpoint regulator in several pathways including the meiotic recombination checkpoint response. Downstream of MEC1, MEK1 is required through its function to inhibit repair between sister chromatids. By contrast, meiotic recombination checkpoint effectors that regulate gene expression and cyclin-dependent kinase activity are not necessary. Phosphorylation of histone H2A, which is catalyzed by Mec1 and the related Tel1 protein kinase in response to DSBs, and can help coordinate activation of the Rad53 checkpoint protein kinase in the mitotic cell cycle, is required for the full checkpoint response. Phosphorylation sites that are targeted by Rad53 in a mitotic S phase checkpoint response are also involved, based on the behavior of cells containing mutations in the DBF4 and SLD3 DNA replication genes. However, RAD53 does not appear to be required, nor does RAD9, which encodes a mediator of Rad53, consistent with their lack of function in the recombination checkpoint pathway that prevents meiotic progression. While this response is similar to a checkpoint mechanism that inhibits initiation of DNA replication in the mitotic cell cycle, the evidence points to a new variation on DNA replication control.

  12. A mutational comparison of adult and adolescent and young adult (AYA) colon cancer.

    Science.gov (United States)

    Tricoli, James V; Boardman, Lisa A; Patidar, Rajesh; Sindiri, Sivasish; Jang, Jin S; Walsh, William D; McGregor, Paul M; Camalier, Corinne E; Mehaffey, Michele G; Furman, Wayne L; Bahrami, Armita; Williams, P Mickey; Lih, Chih-Jian; Conley, Barbara A; Khan, Javed

    2018-03-01

    It is possible that the relative lack of progress in treatment outcomes among adolescent and young adult (AYA) patients with cancer is caused by a difference in disease biology compared with the corresponding diseases in younger and older individuals. There is evidence that colon cancer is more aggressive and has a poorer prognosis in AYA patients than in older adult patients. To further understand the molecular basis for this difference, whole-exome sequencing was conducted on a cohort of 30 adult, 30 AYA, and 2 pediatric colon cancers. A statistically significant difference in mutational frequency was observed between AYA and adult samples in 43 genes, including ROBO1, MYC binding protein 2 (MYCBP2), breast cancer 2 (early onset) (BRCA2), MAP3K3, MCPH1, RASGRP3, PTCH1, RAD9B, CTNND1, ATM, NF1; KIT, PTEN, and FBXW7. Many of these mutations were nonsynonymous, missense, stop-gain, or frameshift mutations that were damaging. Next, RNA sequencing was performed on a subset of the samples to confirm the mutations identified by exome sequencing. This confirmation study verified the presence of a significantly greater frequency of damaging mutations in AYA compared with adult colon cancers for 5 of the 43 genes (MYCBP2, BRCA2, PHLPP1, TOPORS, and ATR). The current results provide the rationale for a more comprehensive study with a larger sample set and experimental validation of the functional impact of the identified variants along with their contribution to the biologic and clinical characteristics of AYA colon cancer. Cancer 2018;124:1070-82. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Low-Dose Radiation Cataract and Genetic Determinants of Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Kleiman, Norman Jay [Columbia University

    2013-11-30

    The lens of the eye is one of the most radiosensitive tissues in the body. Ocular ionizing radiation exposure results in characteristic, dose related, progressive lens changes leading to cataract formation. While initial, early stages of lens opacification may not cause visual disability, the severity of such changes progressively increases with dose until vision is impaired and cataract extraction surgery may be required. Because of the transparency of the eye, radiation induced lens changes can easily be followed non-invasively over time. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue. Despite this observation, considerable uncertainties remain surrounding the relationship between dose and risk of developing radiation cataract. For example, a growing number of human epidemiological findings suggest significant risk among various groups of occupationally and accidentally exposed individuals and confidence intervals that include zero dose. Nevertheless, questions remain concerning the relationship between lens opacities, visual disability, clinical cataract, threshold dose and/or the role of genetics in determining radiosensitivity. Experimentally, the response of the rodent eye to radiation is quite similar to that in humans and thus animal studies are well suited to examine the relationship between radiation exposure, genetic determinants of radiosensitivity and cataractogenesis. The current work has expanded our knowledge of the low-dose effects of X-irradiation or high-LET heavy ion exposure on timing and progression of radiation cataract and has provided new information on the genetic, molecular, biochemical and cell biological features which contribute to this pathology. Furthermore, findings have indicated that single and/or multiple haploinsufficiency for various genes involved in DNA repair and cell cycle checkpoint control, such as Atm, Brca1 or Rad9

  14. Chemical Changes Induced by Irradiation in Meats and Meat Components; Transformations Chimiques Provoquees par les Rayonnements dans les Viandes et Leurs Constituants; Khimicheskie prevrashcheniya v myasnykh produktakh i ikh sostavnykh chastyakh pod vozdejstviem oblucheniya; Alteraciones Quimicas Producidas por Irradiacion de las Carnes y de sus Componentes

    Energy Technology Data Exchange (ETDEWEB)

    Merritt, C. Jr. [Pioneering Research Division, United States Army Natick Laboratories, Natick, MA (United States)

    1966-11-15

    'ju konservacii otrazhaetsja na vkusovyh kachestvah, vyzyvaja pojavlenie specificheskogo privkusa i zapaha. Polagajut, chto jeto ob{sup j}asnjaetsja obrazovaniem letuchih himicheskih soedinenij pri dejstvii radiacii na belki i lipidnye molekuly. Analiz letuchih soedinenij osushhestvljaetsja na gazovom hromatografe s kriogennym ohlazhdeniem do zadannoj temperatury, gde proishodit razdelenie slozhnyh smesej. Identifikacija vydelennyh komponentov provoditsja s pomoshh'ju mass-spektrometrii s bystrym skennirovaniem. Proveden ischerpyvajushhij analjz letuchih soedinenij, vydeljajushhihsja iz govjadiny, svininy, baraniny i teljatiny, kotorye byli oblucheny, a takzhe analiz letuchih soedinenij, obrazujushhihsja pri razlozhenii pod dejstviem obluchenija nekotoryh aminokislot, belkov, zhivotnogo zhira, metilovyh jefirov zhirnyh kislot i trigliceridov. Rezul'taty analizov obluchennyh komponentov mjasnyh produktov sravnivajutsja s rezul'tatami, poluchennymi pri obluchenii samogo mjasa i ego otdel'nyh frakcij, chto daet vozmozh - nost' ustanovit' rol' kazhdoj frakcii v celom. Postulirujutsja mehanizmy obrazovanija letuchih komponentov ot kazhdoj frakcii, a takzhe vzaimodejstvie promezhutochnyh produktov ot razlichnyh frakcij. (author)

  15. Study of reactions of metals with sulphur and phosphorus compounds by pulsed temperatures; Etude des reactions entre metaux et composes du soufre et du phosphore au moyen de brusques hausses de temperature; Issledovanie reaktsii metallov s soedineniyami sery i fosfora pri regulyarnykh izmeneniyakh temperatury; Estudio de reacciones entre metales y compuestos de azufre y de fosforo empleando impulsos de temperatura

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, R B; Grunberg, L [National Engineering Laboratory, East Kilbride, Glasgow (United Kingdom)

    1962-01-15

    , los autores han tenido en cuenta la estructura de los materiales empleados y los procesos de difusion a los que se debe el progreso de la reaccion una vez iniciada esta. (author) [Russian] Protivoiznosnoe dejstvie sernykh i fosfornykh soedinenij, kotorye obychno dobavlyayutsya k mashinnym maslam, zavisit ot khimicheskikh reaktsij s metallicheskimi poverkhnostyami shesterenok. EHti reaktsii imeyut mesto kak pri osnovnoj temperature masel (primerno 100 Degree-Sign C), tak i pri vysokikh temperaturakh (priblizitel'no 600 Degree-Sign C) v techenie nebol'shogo promezhutka vremeni, kogda zubtsy shesterenok vstupayut vo vzai-modejstvie pod nagruzkoj. Temperaturnye izmeneniya sozdavalis' v apparate, v kotorom korotkie impul'sy ehlektrotoka ispol'zovalis' dlya nagrevaniya metallicheskikh provodov, pogruzhennykh v mineral'noe maslo, soderzhashchee v rastvore mechenye soedineniya sery-35 i fosfora-32. Zameryalas' voznikavshaya v provodakh radioaktivnost'. Stepen' reaktsii opredelyalas' kak funktsiya temperatury i vremeni. Rezul'taty reaktsii vyrazhalis' posredstvom osnovnykh zakonov kinetiki. Izucheniyu podverglis' voprosy izmeneniya skorosti reaktsii v zavisimosti ot nalichiya drugikh sostavov v rastvore. Bylo takzhe opredeleno vliyanie predvaritel'no obrazovannykh pokrytij poverkhnosti, soderzhashchikh seru, fosfor, khlor i/ili kislorod. Dlya ob{sup y}asneniya rezul'tatov raboty ispol'zuyutsya dannye o strukture materialov, a takzhe rassmatrivayutsya protsessy diffuzij tam, gde reaktsii vykhodili za svoi nachal'nye stadii. (author)

  16. Preparation of oligonucleotide microarray for radiation-associated gene expression detection and its application in lung cancer cell lines

    International Nuclear Information System (INIS)

    Guo Wanfeng; Lin Ruxian; Huang Jian; Guo Guozhen; Wang Shengqi

    2005-01-01

    , ERCC1, RAD9A, ERCC4 and DNA-PK activities were higher in A549 cells than NCI-H446 cells. Conclusion: These results support a few genes with DNA repair, regulation of cell cycle, cell proliferation and anti-apoptosis as candidates for radioresistance of A549 lung cancer cells. These maybe, provide several gene targets to sensitize the radioresistant cells for improving the radiocurability of lung cancer. (authors)

  17. The molecular basis for cell cycle delays following ionizing radiation. A review

    International Nuclear Information System (INIS)

    Maity, A.; McKenna, W.G.; Muschel, R.J.

    1994-01-01

    Exposure of a wide variety of cells to ionizing (X- or γ-) irradiation results in a division delay which may have several components including a G 1 block, a G 2 arrest or an S phase delay. The G 1 arrest is absent in many cells lines, and the S phase delay is typically seen following relatively high doses (>5 Gy). In contrast, the G 2 arrest is seen in virtually all eukaryotic cells and occurs following high and low doses, even under 1 Gy. The mechanism underlying the G 2 arrest may involve suppression of cyclin B1 mRNA and/or protein in some cell lines and tyrosine phosphorylation of p34 cdc2 in others. Similar mechanisms are likely to be operative in the G 2 arrest induced by various chemotherapeutic agents including nitrogen mustard and etoposide. The upstream signal transduction pathways involved in the G 2 arrest following ionizing radiation remain obscure in mammalian cells; however, in the budding yeast the rad9 gene and in the fission yeast the chk1/rad27 gene are involved. There is evidence indicating that shortening of the G 2 arrest results in decreased survival which has led to the hypothesis that during this block, cells repair damaged DNA following exposure to genotoxic agents. In cell lines examined to date, wildtype p53 is required for the G 1 arrest following ionizing radiation. The gadd45 gene may also have a role in this arrest. Elimination of the G 1 arrest leads to no change in survival following radiation in some cell lines and increased radioresistance in others. It has been suggested that this induction of radioresistance in certain cell lines is due to loss of the ability to undergo apoptosis. Relatively little is known about the mechanism underlying the S phase delay. This delay is due to a depression in the rate of DNA synthesis and has both a slow and a fast component. In some cells the S phase delay can be abolished by staurosporine, suggesting involvement of a protein kinase. Understanding the molecular mechanisms behind these delays

  18. Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao [Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Kabekkodu, Shama Prasada [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India); Fernandes, Donald Jerard [Department of Radiotherapy and Oncology, Shirdi Saibaba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka (India); Vadhiraja, Bejadi Manjunath [Department of Radiation Oncology, Manipal Hospital, Bengaluru, Karnataka (India); Suga, Tomo; Shoji, Yoshimi; Nakayama, Fumiaki; Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Satyamoorthy, Kapaettu, E-mail: ksatyamoorthy@yahoo.com [Department of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka (India)

    2017-01-01

    Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity

  19. Genetic Control of the Trigger for the G2/M Checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Hall, Eric J. [Columbia University; Smilenov, Lubomir B. [Columbia University; Young, Erik F. [Columbia University

    2013-10-01

    The work undertaken in this project addressed two seminal areas of low dose radiation biology that are poorly understood and controversial. These areas are the challenge to the linear-no-threshold (LNT) paradigm at low doses of radiation and, the fundamental elements of radiation bystander effect biology Genetic contributions to low dose checkpoint engagement: The LNT paradigm is an extrapolation of known, measured cancer induction endpoints. Importantly, data for lower doses is often not available. Debatably, radiation protection standards have been introduced which are prudently contingent on the adherence of cancer risk to the established trend seen at higher doses. Intriguing findings from other labs have hinted at separate DNA damage response programs that engage at low or high levels of radiation. Individual radiation sensitivity commensurate with hemizygosity for a radiation sensitivity gene has been estimated at 1-2% in the U.S.. Careful interrogation of the DNA damage response at low doses of radiation became important and served as the basis for this grant. Several genes were tested in combinations to determine if combined haploinsufficiency for multiple radiosensitizing genes could render a cell more sensitive to lower levels of acute radiation exposure. We measured a classical radiation response endpoint, cell cycle arrest prior to mitosis. Mouse embryo fibroblasts were used and provided a uniform, rapidly dividing and genetically manipulable population of study. Our system did not report checkpoint engagement at acute doses of gamma rays below 100 mGy. The system did report checkpoint engagement reproducibly at 500 mGy establishing a threshold for activation between 100 and 500 mGy. Engagement of the checkpoint was ablated in cells nullizygous for ATM but was otherwise unperturbed in cells combinatorially haploinsufficient for ATM and Rad9, ATM and PTEN or PTEN and Rad9. Taken together, these experiments tell us that, in a sensitive fibroblast culture

  20. Disposal of Radioactive Wastes in Natural Salt; Elimination des Dechets Radioactifs dans le Sel Naturel; 0423 0414 ; Evacuacion de Desechos Radiactivos en Formaciones Salinas Naturales

    Energy Technology Data Exchange (ETDEWEB)

    Parker, F. L.; Boegly, W. J.; Bradshaw, R. L.; Empson, F. M.; Hemphill, L.; Struxness, E. G.; Tamura, T. [Health Physics Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1960-07-01

    pueden solo estudiarse en las formaciones salinas inalteradas. En un yacimiento estratificado de sal situado en Hutchinson, Kansas, se han hecho experimentos con modelos a escala 1:5 y se estan realizando pruebas sobre el terreno a escala 1:1. (author) [Russian] Predlagaemoe ispol'zovanie polostej soljanyh zalezhej v kachestve mest dlja udalenija radioaktivnyh othodov osnovyvaetsja na: 1. Sushhestvovanii soli v techenie geologicheskih vekov, 2. Vodonepronicaemosti soli, 3. Shirokom geologicheskom rasprostranenii soli, 4. Chrezvychajno bol'shih kolichestvah imejushhejsja soli, 5. Strukturnoj prochnosti soli, 6. Sravnitel'no vysokoj teploprovodnosti soli po sravneniju s drugimi geologicheskimi obrazovanijami obshhek haraktera, 7. Vozmozhnom ispol'zovanii cennyh rasshhepljajushhihsja produktov v othodah, vvedennyh v sol', J 8. Sravnitel'no legkom sozdanii polostej v soli putem vyemki porody i eshhe bol'shej legkosti i nizkih zatratah na razrabotku v soli rastvornyh polostej, 9. Nizkoj sejsmichnosti v rajonah glavnyh soljanyh zalezhej. Zhidkie radioaktivnye othody mogut hranit'sja v polostjah, nahodjashhihsja . v zalezhah prirodnoj soli, esli strukturnye svojstva soli ne narusheny himicheskim vzaimodejstviem, davleniem, temperaturoj ili radiaciej. Analiticheskie issledovanija pokazyvajut, chto mozhno hranit' 800 gal/tonn dvuhgodichnyh othodov na 10000 MWD/T v sfere diametrom 10 futov, esli temperatura ne. prevyshaet 200 Degree-Sign po Farengejtu. Laboratornye ispytanija pokazyvajut, chto strukturnye svojstva i teploprovodnost' gornoj soli ne izmenjajutsja v znachitel'noj stepeni pod vozdejstviem vysokih doz radiacii, hotja vysokie temperatury uvelichivajut stepen' polzuchesti kak dlja obluchennyh, tak i dlja neobluchennyh obrazcov. Himicheskoe vzaimodejstvie zhidkih othodov s sol'ju daet hlor i drugie hloristye gazoobraznye soedinenija, no ih kolichestvo ne veliko. Migracija nuklidov v soli i deformacija polosti i kamery mogut byt' izucheny tol'ko v netronutoj zalezhi soli

  1. Thermal Annealing of Paramagnetic Defects Induced by Gamma Irradiation in (NH{sub 4}){sub 2}SO{sub 4} and (ND{sub 4}){sub 2}SO{sub 4} Single Crystals: Experimental Verification of the Theory of Fletcher and Brown; Recuit Thermique des Defauts Paramagnetiques Induits par Irradiation Gamma dans des Monocristaux de (NH{sub 4}){sub 2}SO{sub 4} et (ND{sub 4}){sub 2}SO{sub 4}: Verification Experimentale de la Theorie de Fletcher et Brown; 0422 0415 0420 041c 0414 ; Regeneracion Termica de los Defectos Paramagneticos Inducidos por Irradiacion Gamma en Monocristales de (NH{sub 4}){sub 2}SO{sub 4} y (ND{sub 4}){sub 2}SO{sub 4}: Verificacion Experimental de la Teoria de Fletcher y Brown

    Energy Technology Data Exchange (ETDEWEB)

    Calusaru, A.; Barbur, I.; Ursu, I. [Institut de Physique Atomique, Bucarest (Romania); Universite ' Babes' , Cluj (Romania)

    1965-04-15

    kinetika s edinym plato, sootvetstvujushhim obshhej rekombinacii radikalov. Dlja kazhdoj izotermy predstavljaetsja vozmozhnym sostavit' sootvetstvujushhee uravnenie, ispol'zuja pri jetom funkciju oshibok, vyvedennuju Fletcherom i Braunom pri rassmotrenii modeli i rekombinacii par, vnachale korrelirovannyh, a zatem vydelennyh v sootvetstvii s processom besporjadochnogo dvizhenija. Posle ispravlenija jetoj funkcii s uchetom kojefficienta q dannaja funkcija byla privedena v sootvetstvie s opytom. Sostavnaja krivaja otzhiga ochen' horosho otrazhaet funkciju ispravlennyh oshibok. Pri primenenii fenomenologicheskogo metoda Fletchera i Brauna dlja rascheta jenergii aktivacii bylo najdeno znachenie 1,594 jev, sootvetstvujushhee pervomu radikalu v (NH{sub 4}){sub 2}SO{sub 4}. Ispol'zuja izmenenie kojefficienta diffuzii'v zavisimosti ot temperatury, dlja toj zhe jenergii aktivacii bylo ustanovleno znachenie v 1,592 jev. S pomoshh'ju metoda Vand-Primak bylo najdeno znachenie v 1,45 jev, kotoroe javljaetsja men'shim po sravneniju s dvumja predydushhimi. V zakljuchenie otmechaetsja, chto model' rekombinacii par, korrelirovannyh v sootvetstvii s processom besporjadochnogo dvizhenija, primenima v forme, privedennoj v teorii, kogda imeetsja dovol'no slaboe vzaimodejstvie mezhdu obrazovavshimisja vidami i reshetkoj; takim putem pervonachal'no korrelirovannye pary mogut byt' vydeleny. (author)

  2. Interesting Developments in UO{sub 2} Technology; Progres interessants dans la technologie du bioxyde d'uranium; Interesnye usovershenstvovaniya tekhnologii UO{sub 2}; Recientes progresos en la tecnologia del UO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, J. A.L. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)

    1963-11-15

    permitiran determinar si las nuevas formas de combustible pueden ofrecer alguna ventaja economica. Mientras tanto, el continuo perfeccionamiento de las barras combustibles de UO{sub 2} sinterizado en geometrias simples dara lugar a una renida competencia. (author) [Russian] Sejchas, kogda neskol'ko reaktorov, v kotorykh toplivom sluzhit UO{sub 2}, nakhodyatsya v postoyannoj ehkspluatatsii, khoroshie radiatsionnye -svojstva UO{sub 2} ne nuzhdayutsya v dokazatel'stve. Priyatno uznavat' o tom, chto vazhnye usovershenstvovaniya eshche poyavlyayutsya. Naibolee znachitel'nom za poslednee vremya yavilos' otkrytie sotrudnikami istituta Behttely ochen' vysokoj teploprovodnosti otdel'nogo odinochnogo kristalla UO{sub 2} pri povyshennykh temperaturakh. Provedennoe v svyazi s raskhozhdeniem mnenij po ehtomu voprosu obluchenie v Chok-Rivere pokazalo, chto bol'shie zerna, obrazuyushchiesya v rabotavshikh toplivnykh ehlementakh, ne obyazatel'no obladayut ehtoj povyshennoj provodimost'yu. Ehksperimenty nashej laboratorii pokazali, chto povyshenie imeet mesto tol'ko v podstekhiometricheskikh soedineniyakh i malo zavisit, esli voobshche zavisit, ot otsutstviya granits zeren. Bezuslovno, vysokaya provodimost' mozhet byt' poluchena v polikristallicheskikh spekshikhsya materialakh putem regulirovaniya stekhiometrii. Davno izvestno, chto udlinenie obolochki mozhno umen'shit', esli izgotovit' tabletki ieh UO{sub 2} s uglubleniyami na tortsovykh poverkhnostyakh. Pozzhe bylo pokazano, chto smeshcheniyu topliva v pustoe prostranstvo v kontse trubki s tabletkami meshaet diametral'noe rasshirenie topliva i ego mekhanicheskoe vzaimodejstvie s obolochkoj. Samym bol'shim dostizheniem v otnoshenii svedeniya k minimumu rasshireniya obolochki yavilos' uyasnenie togo, chto prodol'noe, i diametral'noe rasshireniya vzaimosvyazany cherez posredstvo ob{sup e}mnogo rasshireniya topliva, goryachaya serdtsevina kotorogo dovol'no plastichna. Rasshirilis' nashi prakticheskie znaniya faktorov, opredelyayushchikh

  3. Inelastic Neutron Scattering from Doped Germanium and Silicon; Diffusion Inelastique des Neutrons dans du Germanium et du Silicium Contenant une 'Impurete'; Neuprugoe rasseyanie nejtronov na germanii i kremnii s prisadkoj; Dispersion Inelastica de Neutrones en Germanio y Silicio Deliberadamente Impurificados

    Energy Technology Data Exchange (ETDEWEB)

    Dolling, G. [Chalk River Nuclear Laboratories, Chalk River, ON (Canada)

    1965-04-15

    experimental. En los casos mas favorables, esta exactitud (relativa) alcanza al 0,5% del valor de la frecuencia, y llega hasta 2,0 Degree-Sign Inverted-Exclamation-Mark o tratandose de algunos modos opticos longitudinales en el silicio. (author) [Russian] Normal'nye formy kolebanija chistyh poluprovodnikov germanija i kremnija shiroko izuchalis' s pomoshh'ju kogerentnogo odnofononnogo rassejanija medlenny nejtronov na mono-kristallicheskih obrazcah. V dannom doklade opisyvajutsja analogichnye jeksperimenty, vypolnennye 1) s germaniem s bol'shoj prisadkoj ( Tilde-Operator 0,1%) a) mysh'jaka i '') galija, a takzhe 2) s kremniem s fosfornoj prisadkoj. V kazhdom sluchae kontrol'nye jeksperimenty provodilis' na kristallah vysokoj chistoty. Vse izmerenija vypolnjalis' na trehosnom kristallicheskom spektrometre v laboratorijah v Chok- River. Kak izvestno, postojannaja uprugosti C{sub 44} dlja germanija v znachitel'noj stepeni zavisit ot koncentracii prisadki, i pojetomu nekotorye poperechnye akusticheskie koljobanija (TA) s bol'shoj dlinoj volny izuchalis' s cel'ju vyjasnenija nalichija takih jeffektov v dispergirujushhej oblasti. Drugie TA kolebanija, chastoty kotoryh mozhno izmerjat' s vysokoj stepen'ju tochnosti, takzhe izuchalis' v oboih materialah s cel'ju vozmozhno bolee tochnoj proverki nebol'shih jeffektov, kotorye mozhno bylo by pripisat' nalichiju izbytka jelektronov ili dyrok. Osobenno tshhatel'no izuchalis' kolebanija so sledujushhimi volnovymi vektorami (aq/2{pi}, gde a -storona kubicheskoj jelementarnoj jachejki): 1) v germanii (1; 0; 0); 2) v kremnii (0.85; 0.85; 0) i (0.3; 0;0). Mozhno bylo by predpolozhit', chto takie normal'nye kolebanija projavjat neobychnye cherty v kristallah n-nogo tipa, poskol'ku dlja rassejanija jelektronov mezhdu sosednimi minimumami zon provodimosti potrebovalos' by vzaimodejstvie dlja sohranenija {sup i}mpul'sa kristalla{sup .} Rezul'taty vo vseh sluchajah byli otricatel'nymi, t.e. v predelah tochnosti jeksperimentov ne nabljudalos' nikakih

  4. Instability and Related Macroscopic Effects in Toroidal Discharges; Instabilites et Effets Macroscopiques qui les Accompagnent dans les Decharges Toroidales; Neustojchivost' i svyazannye s nej makroskopicheskie ehffekty v toroidal'nykh razryadakh; Inestabilidad y Efectos Macroscopicos Conexos, en las Descargas Toroidales

    Energy Technology Data Exchange (ETDEWEB)

    Kadomcev, B. B.; Pogutse, O. P. [Institut Atomnoj Ehnergii Im. I.V. Kurchatova, Moskva, SSSR (Russian Federation)

    1966-04-15

    perenositsja konvekciej. Pri ochen' sil'nom magnitnom pole konvekcionnye jachejki perekryvajutsja mezhdu soboj, i makroskopicheskie potoki tepla i chastic mogut znachitel'no prevoshodit' klassicheskie potoki, opredeljaemye parnymi stolknovenijami Priuvelichenii davlenija plazmy konvekcionnye jachejki perestajut perekryvat'sja, i makroskopicheskij jeffekt ot tokovokonvektivnoj neustojchivosti stanovitsja malym. Pri eshhe bol'shem davlenii plazmy neustojchivye kolebanija stanovjatsja nepotencial'nymi i soprovozhdajutsja iskrivleniem silovyh linij, vsledstvie kotorogo proishodit perestrojka magnitnyh poverhnostej. Narjadu s tokovokonvektivnoj neustojchivost'ju v plazme nizkogo davlenija razvivaetsja drejfovaja neustojchivost', dlja kotoroj takzhe provedeno nelinejnoe rassmotrenie. Rassmotreno vzaimodejstvie drejfovyh kolebanij s konvekcionnymi jachejkami. (author)

  5. The Digital Autofluoroscope; L'Autofluoroscope Numerique; Tsifrovoj avtofluoroskop; Autofluoroscopio Numerico

    Energy Technology Data Exchange (ETDEWEB)

    Bender, M. A. [Roswell Park Memorial Institute, Buffalo, NY (United States)

    1964-10-15

    podhodjat k drugoj fototrubke. Impul'sy, voznikajushhie odnovremenno v ljuboj pare iz 35 fototrubok, v ravnoj mere dostigajut kristalla, v kotorom proishodit vzaimodejstvie. Pozicionnyj signal, voznikshij v fototrubke, ne zavisit ot vysoty impul'sa. Kontury antisovpadenija otvodjat odnovremennye impul'sy, voznikajushhie vrezul'tatev zaim od ej stvi ja Komptona, za kotorym sleduet absorbcija rassejannogo izluchenija v sosednem kristalle. Cifrovoj harakter si st emy svetovy h trubok horosho prisposoblen k hraneniju na magnitnom serdechnike s posledujushhim nepreryvnym schityvaniem bezrazrushenija pokazanij na polnorazmernoj katodno-luchevoj trubke ili k cifrovomu vypisyvaniju dlja kolichestvennogo analiza. Pervym preimushhestvom avtofluoroskopa nad radioizotopnymi skennerami javljaetsja znachitel'noe sokrashhenie vremeni, neobho dim o go dlja issledovanija. Pri ravnoj sistem e doz opuholi mozga i pecheni obnaruzhivajutsja v techenie 0,1 vremeni, neobhodimogo dlja obychnogo skennirovanija. Vtoroe preimushhestvo svjazano s t em , chto predostavljaetsja informacija obo vsem organe. Jeto daet vozmozhnost' prosledit' dinamicheskie processy vizual'no i ispol'zovat' izotopy ili mechenye soedinenija, imejushhie ochen' korotkie periody poluraspada i poluvyvedenija. S umen'sheniem perioda poluraspada mozh et byt' proi zv eden o sootv et s tv ujushh e e uvelichenie vvodimoj d ozy , rezul' tat om ch e go javljaetsja sokrashhenie vremeni obsledovanija. Vremja o b luchenija mozhet byt' takim korotkim, chto v nastojashhee vremja stali ispol'zovat' kinofoto- graficheskie metody dlja vizual'nogo nabljudenija i kolichestvennogo opredelenija prohozhdenija gippurana mechenogo, jodom-131, cherez pochki i bariem-137 cherez polosti serdca. (author)

  6. Strain Dependence of the Frequencies and the Thermal Expansion of the Hexagonal Close-Packed Lattice; Variations, en Fonction de la Deformation, des Frequences et de la Dilatation Thermique du Reseau a Structure Hexagonale Compacte; Zavisimost' chastot i teplovogo rasshireniya geksagonal'noj reshetki s plotnoj upakovkoj ot napryazheniya; Variacion de las Frecuencias y de la Dilatacion Termica de la Red Hexagonal Compacta en Funcion de la Deformacion

    Energy Technology Data Exchange (ETDEWEB)

    Srinivasan, R.; Ramji Rao, R. [Physics Department, Indian Institute of Technology, Madras (India)

    1965-04-15

    }{sub 6} ot vysheukazannyh naprjazhenij. Byli ustanovleny verhnie i nizhnie temperaturnye predely jekvivalentnyh parametrov Grjunajzena ''{gamma}G i {gamma}'' dlja treh par znachenij tip. Ustanovleno, chto {gamma}' = {gamma}'' i chto verhnij temperaturnyj predel 7 Inverted-Question-Mark bol'she nizhnego temperaturnogo predela {gamma}' primerno v 0,3 raza. Velichina jetoj raznicy, okazyvaetsja, ne zavisit ot znachenij tip. Uchityvaja vzaimodejstvie so sledujushhim sosednim chlenom, mozhno ozhidat' umen'shenija jetoj raznicy. Jeti teoreticheskie rezul'taty sopostavljajutsja s rezul'tatami jeksperimentov s magniem. (author)

  7. Use of the Neutron Die-Away Technique to Test Control Rod Effectiveness Theories; Emploi de la Methode d'Absorption des Neutrons pour Verifier les Theories sur l'Efficacite des Barres de Commande; Ispol'zovanie metoda spada potoka nejtronov dlya proverki teorij ehffektivnosti reguliruyushchikh sterzhnej; Aplicacion de la Tecnica de Extincion Neutronica a la Verificacion de las Teorias sobre la Eficacia de las Barras de Control

    Energy Technology Data Exchange (ETDEWEB)

    Perez, R. B. [University of Florida, Gainesville, FL (United States); De Saussure, G.; Silver, E. G. [University of Florida, Gainesville, FL (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    1964-04-15

    pomoshh'ju shemy Nordhejma -Skalettara i koda diffuzii byli vyshe jeksperimental'nyh rezul'tatov pochti na 10% . Odnako vzaimodejstvie mezhdu tolstymi sterzhnjami bylo pravil'no predskazano s pomoshh'ju oboih metodov. Dlja tonkih sterzhnej chrezvychajno tochnye rezul'taty byli polucheny po metodu Nordhejma- Skalettara. Rashozhdenija rezul'tatov dlja tolstyh sterzhnej sleduet ozhidat' v teh sluchajah, kogda dlja opisanija jeffektov poglotitelej, imejushhih razmery sechenij, sravnimye so srednim svobodnym probegom nejtrona v zamedlitele, ispol'zuetsja teorija diffuzii. Chtoby opredelit' tochku, v kotoroj teorija diffuzii stanovitsja neprigodnoj, vypolnjajutsja izmerenija so sterzhnjami promezhutochnyh razmerov. (author)

  8. Joule Heating of Plasma in the Toroidal Tokamak-3 Device; Chauffage du Plasma par Effet Joule, dans l'Installation Torique; Dzhoulev nagrev plazmy na toroidal'noj ustanovke Tokamak-3; Calentamiento de un Plasma por Efeto Joule en la Instalacion Toroidal Tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Arcimovich, L. A.; Afrosimov, V. V.; Gladkovskij, I. P.; Mirnov, S. V.; Petrov, M. P.; Strelkov, V. S. [Institut Atomnoj Ehnergii, Im. I.V. Kurchatova, Moskva, SSSR (Russian Federation)

    1966-04-15

    jekvatorial'noj ploskosti tora i nabljudalsja drejf plazmennogo shnura ''naruzhu'' (uvelichenie bol'shogo radiusa vitka). Jeto dvizhenie mozhet byt' vyzvano izmeneniem radiusa tokovogo shnura, nagrevom plazmy ili zatuhaniem tokov Fuko v provodjashhem kozhuhe. V jetih uslovijah na ustanovke Tokamak-3 udalos' poluchit' makroskopicheski ustojchivyj plazmennyj shnur, odnako temperatura plazmy okazalas' men'she, chem. sledovalo ozhidat' pri otsutstvii anomal'nyh poter' jEhnergii. K bol'shim poterjam jEhnergii dolzhny privodit' processy, proishodjashhie pri vzaimodejstvii plazmennogo shnura s diafragmoj. Jeto vzaimodejstvie udalos' oslabit', primeniv diafragmu special'noj formy i ispol'zovav svojstvo shnura smeshhat'sja naruzhu v techenie processa. Zadachej issledovanij javljalos' opredelenie razlichnyh parametrov plazmy v jetih uslovijah, v tom chisle jelektronnoj i ionnoj temperatur. Dlja opredelenija jelektronnoj temperatury po izmeneniju soprotivlenija plazmy neobhodimo, krome jelektricheskih harakteristik shnura znat' zakon izmenenija vo vremeni radiusa shnura. Reshenie na schetnoj mashine sistemy uravnenij, vkljuchajushhej jelektrotehnicheskoe uravnenie i uravnenie ravnovesija, pozvoljaet opredelit' izmenenie vo vremeni temperatury plazmy i ee koncentracii, a takzhe radiusa i smeshhenija plazmennogo shnura na osnovanii, jeksperimental'no izmerennyh zavisimostej ot vremeni toka v plazme, naprjazhenija, signalov magnitnyh zondov i radiointerferometra. Vychislennaja funkcija temperatury vozrastaet za vremja processa i dostigaet 100-200 jev. Spektroskopicheskie izmerenija jelektronnoj temperatury dajut znachenija blizkie k vychislennym. Rezul'taty izmerenij jenergeticheskogo spektra potoka bystryh nejtral'nyh atomov horosho soglasujutsja s predlozheniem o tom, chto spektr ionov plazmy blizok k maksvellovsko- mu s temperaturoj okolo 100 jev. Sushhestvennoe otklonenie haraktera spektra ot maksvel- lovskogo nabljudaetsja v neustojchivom rezhime razrjada v momenty, sootvetstvujushhie

  9. Fabrication and Testing of Prototype APM-Clad UO{sub 2} Fuel Elements; Fabrication et essai de prototypes de cartouches de combustible en bioxyde d'uranium gaine d'aluminium (APM); Izgotovlenie i ispytanie prototipa toplivnykh ehlementov na osnove UO{sub 2} s obolochkoj iz alyuminiya metodom poroshkovoj metallurgii; Elaboracion y ensayo de elementos combustibles prototipo de UO{sub 2} con revestimiento de aluminio sinterizado

    Energy Technology Data Exchange (ETDEWEB)

    Ballif, III, J. L.; Friske, W. H.; Gordon, R. B. [Atomics International, Canoga Park, California (United States)

    1963-11-15

    los elementos combustibles se extrajeron del reactor a raiz de problemas suscitados por el instrumental utilizado para los ensayos. Los tres elementos restantes continuaban en el reactor. Todos los resultados de los experimentos realizados hasta la fecha parecen indicar que el sistema de combustible PMA-UO{sub 2} permitira alcanzar los objetivos fijados para el programa relativo al reactor POPR. (author) [Russian] V podderzhku Programmy prototipov organicheskikh ehnergoreaktorov (POPR) moshchnost'yu 50 mgvt (ehl.) byla provedena obshirnaya rabota po razrabotke poroshkovoj metallurgiej alyuminievykh materialov (APM) v kachestve obolochek dlya topliva iz UO{sub 2} . Kak chast' ehtoj raboty byli issledovany ehvteticheskoe soedinenie, svarke v styk oplavleniem i kholodnaya svarka. Kolduehlla pod davleniem kak metody dlya soedineniya stykov pri sborke toplivnykh ehlementov. Vibratsionnoe uplotnenie izuchalos' kak sredstvo zapolneniya trubok APM dvuokis'yu urana. Opyty vne reaktora provodilis' dlya.ogo, chtoby poluchit' informatsiyu o svomestimosti APM - UO{sub 2} . Ehta rabota pokazala, chto pri sushchestvuyushchikh usloviyakh ehvteticheskoe soedinenie yavlyaetsya naibolee podkhodyashchim sposobom dlya soedineniya stykov; vibratsionnoe uplotnenie davalo plotnost' topliva v predelakh ot 80 do 88% teoreticheskoj plotnosti, i ne nablyudalos' vzaimodejstvie APM -UO{sub 2} v diapazone ehkspluatatsionnykh temperatur POPR (temperatura poverkhnosti razdela toplivo - obolochka maksimum 850{sup o}F). V rezul'tate ehtoj raboty bylo izgotovleno 5 prototipov UO{sub 2}-APM toplivnykh ehlementov s tsel'yu ispytaniya na opytnom reaktore s organicheskim zamedlitelem. Kazhdyj ehlement sostoyal iz 24 ili 25 toplivnykh sterzhnej v obolochke iz APM i sgruppirovannykh v sistemu 5 x 5 v stal'noj korobke, pokrytoj nikelem, ili toplivnoj korobke ieh APM. Dlya togo, chtoby uvelichit' poverkhnost' ehlementa i tem samym znachitel'no uluchshit' teploperedachu, izgotovlennaya ehkstruziej obolochka ieh