We are investigating the unique chromosomal metabolic events associated with meiosis and the repair of chromosomes following exposure to DNA damaging events in the yeast Saccharomyes cerevisiae. Many of the genes necessary for the repair of DNA double strand breaks (DSB) are required for the successful completion of the meiotic cycle suggesting that both processes proceed through similar molecular mechanisms. A central component for both the repair of DSBs and the successful completion of meiosis is the protein encoded by the RAD52 gene. In addition to its role in DSB repair and meiosis, RAD52 appears to influence spontaneous mitotic recombination. In strains carrying a complete deletion of the RAD52 gene mitotic recombination between repeats is reduced; however, this decrease is blocked by a concomitant mutation in the gene encoding the Rho-associated nuclease RhoNUC (RNC1). This result suggests that RNC1 is epistatic to RAD52 for spontaneous mitotic recombination. Interestingly rnc1 does not rescue the DSB repair deficiency or the meiotic lethality associated with rad52. The possible role of RAD52 during replication is also being investigated. Using a unique system whereby we measure the frequency of """"""""excision"""""""" of a bacterial transposon Tn5 placed into the yeast LYS2 gene, we have found that mutations in the gene encoding DNA polymerase I or III lead to high levels of Tn5 """"""""excision"""""""". The elevated levels of """"""""excision"""""""" seen in polIII or polI strains is reduced when a null mutant of RAD52 is introduced into these strains. This suggests an interaction between the enzymes proposed to be responsible for DNA lagging strand synthesis and RAD52. RNC1 does not appear to play a role in this interaction since rnc1 rad52 polIII mutants are still blocked for Tn5 """"""""excision"""""""".

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES065073-04
Application #
3755485
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Westmoreland, James W; Mihalevic, Michael J; Bernstein, Kara A et al. (2018) The global role for Cdc13 and Yku70 in preventing telomere resection across the genome. DNA Repair (Amst) 62:8-17
Sagi, Dror; Marcos-Hadad, Evgeniya; Bari, Vinay K et al. (2017) Increased LOH due to Defective Sister Chromatid Cohesion Is due Primarily to Chromosomal Aneuploidy and not Recombination. G3 (Bethesda) 7:3305-3315
Westmoreland, James W; Resnick, Michael A (2016) Recombinational repair of radiation-induced double-strand breaks occurs in the absence of extensive resection. Nucleic Acids Res 44:695-704
Godin, Stephen K; Zhang, Zhuying; Herken, Benjamin W et al. (2016) The Shu complex promotes error-free tolerance of alkylation-induced base excision repair products. Nucleic Acids Res 44:8199-215
Sakofsky, Cynthia J; Roberts, Steven A; Malc, Ewa et al. (2014) Break-induced replication is a source of mutation clusters underlying kataegis. Cell Rep 7:1640-1648
Roberts, Steven A; Gordenin, Dmitry A (2014) Clustered and genome-wide transient mutagenesis in human cancers: Hypermutation without permanent mutators or loss of fitness. Bioessays 36:382-393
Covo, Shay; Chiou, Eric; Gordenin, Dmitry A et al. (2014) Suppression of allelic recombination and aneuploidy by cohesin is independent of Chk1 in Saccharomyces cerevisiae. PLoS One 9:e113435
Lujan, Scott A; Clausen, Anders R; Clark, Alan B et al. (2014) Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition. Genome Res 24:1751-64
Roberts, Steven A; Lawrence, Michael S; Klimczak, Leszek J et al. (2013) An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers. Nat Genet 45:970-6
Chan, Kin; Resnick, Michael A; Gordenin, Dmitry A (2013) The choice of nucleotide inserted opposite abasic sites formed within chromosomal DNA reveals the polymerase activities participating in translesion DNA synthesis. DNA Repair (Amst) 12:878-89

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