MMS1 protects against replication-dependent DNA damage in Saccharomyces cerevisiae.
A series of yeast mutants were isolated that are sensitive to killing by the monofunctional DNA-alkylating agent methyl methanesulfonate (MMS) but not by UV or X-radiation. We have cloned and characterized one of the corresponding genes, MMS1, and show that the mms1 Delta mutant is dramatically sensitive to killing by MMS and mildly sensitive to UV radiation. mms1 Delta mutants display an elevated level of spontaneous DNA damage and genomic instability. Furthermore, the mms1 Delta cells are sensitive to killing by conditions that induce replication-dependent double-strand breaks, such as treatment with camptothecin, and incubation of a cdc2-2 strain at the restrictive temperature. rad52 Delta is epistatic to mms1 Delta for MMS and camptothecin sensitivity, indicating that Mms1 acts in concert with Rad52. However, unlike mutants of the RAD52 group, mms1 Delta cells are not sensitive to gamma-rays, which induce double-strand breaks independently of DNA replication. Together these results suggest a role for an Mms1-dependent, Rad52-mediated, pathway in protecting cells against replication-dependent DNA damage.
Hryciw
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Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada, S7K 0M7.
Tang
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Fontanie
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Xiao
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D003001:Cloning, Molecular; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics; D004843:Epistasis, Genetic; D005800:Genes, Fungal; D008741:Methyl Methanesulfonate / Q000633:toxicity*; D009154:Mutation; D010641:Phenotype; D051721:Rad52 DNA Repair and Recombination Protein; D015183:Restriction Mapping; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
D004268:DNA-Binding Proteins; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate