role of mismatch repair in the prevention of base pair mutations in Saccharomyces cerevisiae

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (26), p.15487-15491
• Main Authors: Earley, M.C, Crouse, G.F
• Format: Article
• Language: English
• Subjects: aerobic conditions; Aerobiosis; anaerobic conditions; Anaerobiosis; assays; Base Pair Mismatch - genetics; Biological Sciences; Cell growth; Cell lines; cyc1 gene; cytochrome c; Diploidy; DNA Damage; DNA mismatch repair; DNA Repair; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Escherichia coli; Fungal Proteins - genetics; Fungal Proteins - metabolism; Gene Deletion; genes; genetic change; Genetic mutation; Genetics; Human genetics; msh2 gene; msh3 gene; msh6 gnee; Mutation; MutS Homolog 2 Protein; MutS Homolog 3 Protein; Plasmids; Point Mutation; prevention; Radiation damage; reversion rates; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae Proteins; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.26.15487

In most organisms, the mismatch repair (MMR) system plays an important role in substantially lowering mutation rates and blocking recombination between nonidentical sequences. In Saccharomyces cerevisiae, the products of three genes homologous to Escherichia coli mutS-MSH2, MSH3,and MSH6-function in MMR by recognizing mispaired bases. To determine the effect of MMR on single-base pair mismatches, we have measured reversion rates of specific point mutations in the CYC1 gene in both wild-type and MMR-deficient strains. The reversion rates of all of the point mutations are similar in wild-type cells. However, we find that in the absence of MSH2 or MSH6, but not MSH3, reversion rates of some mutations are increased by up to 60,000-fold, whereas reversion rates of other mutations are essentially unchanged. when cells are grown anaerobically, the reversion rates in MMR-deficient strains are decreased by as much as a factor of 60. We suggest that the high reversion rates observed in these MMR-deficient strains are caused by misincorporations opposite oxidatively damaged bases and that MMR normally prevents these mutations. We further suggest that recognition of mispairs opposite damaged bases may be a more important role for MMR in yeast than correction of errors opposite normal bases.