Enzymes Involved in DNA Repair and Meiosis

Resnick, M A.

Abstract

All eucaryotic cells can experience breaks within their chromosomes which must be repaired efficiently to retain viability. Such broken chromosomes arise both spontaneously and after exposure to endogenous and exogenous agents. Treatments which have been shown to cause DNA strand breaks include physical agents (e.g. X-rays) and chemical agents (e.g. methylmethane sulfonate, anti-tumor drugs such as phleomycin or bleomycin, etc.). Double-strand breaks within DNA stimulate mutagenesis, recombination, and aneuploidy and are, therefore, implicated in the etiology of both carcinogenesis and aging. The model eucaryote Saccharomyces cerevisiae has been used to study genes involved in the repair of broken chromosomes and which mediate recombination events that occur during normal mitotic growth. Several genes known to be involved in these processes (including rad50, rad51, rad52, and others) have been characterized in great detail. In addition, several newly identified mutants have been shown to affect the same pathways of DNA repair and recombination. These mutants have been analyzed for their sensitivity to specific mutagens, spontaneous and induced recombination proficiency, and their ability to repair DNA strand breaks induced by in vivo expression of the HO, EcoRI, and PvuII endonucleases.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES021016-14
• Application #: 5202094
• Support Year: 14
• Fiscal Year: 1995

Institution

• Name: National Institute of Environmental Health Sciences
• Country: United States

Publications

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

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

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; 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