We are investigating the unique metabolic events associated with meiotic recombination and the repair of chromosomes following exposure to DNA damaging events in the budding yeast Saccharomyces cerevisiae. Many genes necessary for the repair of DNA double strand breaks (DSB) are also required for the successful completion of meiosis, suggesting that these processes have similar molecular mechanisms. The RAD52 gene plays a prominent role in meiosis and in repair of DSB's and is under active investigation. An additional yeast gene, RNC1, has been cloned and sequenced in the lab and shown to influence recombination and repair in a RAD52-dependent manner. Recent work has focused on: 1. biochemical study of nuclease protein purified from overexpressing E. coli and yeast cells; 2. the physiological effects of expression of mutant nuclease enzymes with altered GTPase activities in wild-type and repair-deficient yeast cells; 3. characterization of several recently identified yeast genes whose expression is lethal in rad52-deleted strains (yeast strains which cannot repair DSB's); 4. analysis of a newly identified class of mutant yeast cells which are deficient in DSB repair and/or mitotic recombination.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Intramural Research (Z01)
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Andres, Sara N; Appel, C Denise; Westmoreland, James W et al. (2015) Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair. Nat Struct Mol Biol 22:158-66
Ma, Wenjian; Westmoreland, Jim W; Gordenin, Dmitry A et al. (2011) Alkylation base damage is converted into repairable double-strand breaks and complex intermediates in G2 cells lacking AP endonuclease. PLoS Genet 7:e1002059
Nakai, Wataru; Westmoreland, Jim; Yeh, Elaine et al. (2011) Chromosome integrity at a double-strand break requires exonuclease 1 and MRX. DNA Repair (Amst) 10:102-10
Argueso, Juan Lucas; Westmoreland, James; Mieczkowski, Piotr A et al. (2008) Double-strand breaks associated with repetitive DNA can reshape the genome. Proc Natl Acad Sci U S A 105:11845-50
Chen, Ling; Trujillo, Kelly M; Van Komen, Stephen et al. (2005) Effect of amino acid substitutions in the rad50 ATP binding domain on DNA double strand break repair in yeast. J Biol Chem 280:2620-7
Resnick, Michael A (2005) Reduced replication: a call to ARMS. Cell 120:569-70
Lewis, L Kevin; Karthikeyan, G; Cassiano, Jared et al. (2005) Reduction of nucleosome assembly during new DNA synthesis impairs both major pathways of double-strand break repair. Nucleic Acids Res 33:4928-39
Lewis, L Kevin; Lobachev, Kirill; Westmoreland, James W et al. (2005) Use of a restriction endonuclease cytotoxicity assay to identify inducible GAL1 promoter variants with reduced basal activity. Gene 363:183-92
Lewis, L Kevin; Storici, Francesca; Van Komen, Stephen et al. (2004) Role of the nuclease activity of Saccharomyces cerevisiae Mre11 in repair of DNA double-strand breaks in mitotic cells. Genetics 166:1701-13
Lobachev, Kirill; Vitriol, Eric; Stemple, Jennifer et al. (2004) Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr Biol 14:2107-12

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