Negative epistasis between natural variants of the Saccharomyces cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair.

ABSTRACT: In budding yeast, the MLH1-PMS1 heterodimer is the major MutL homolog complex that acts to repair mismatches arising during DNA replication. Using a highly sensitive mutator assay, we observed that Saccharomyces cerevisiae strains bearing the S288c-strain-derived MLH1 gene and the SK1-strain-derived PMS1 gene displayed elevated mutation rates that conferred a long-term fitness cost. Dissection of this negative epistatic interaction using S288c-SK1 chimeras revealed that a single amino acid polymorphism in each gene accounts for this mismatch repair defect. Were these strains to cross in natural populations, segregation of alleles would generate a mutator phenotype that, although potentially transiently adaptive, would ultimately be selected against because of the accumulation of deleteriou

SUBMITTER: Heck JA 

PROVIDER: S-EPMC1413905 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature