Requirement for DNA mismatch repair proteins in the transcription-coupled repair of thymine glycols in Saccharomyces cerevisiae

Abstract

Defects in DNA mismatch repair have been shown to lead to increased genomic instability and mutability. We recently found that human cells defective in the DNA mismatch repair gene, hMSH2, were deficient in the transcription-coupled repair (TCR) of both oxidative DNA damage, including thymine glycols, and UV-induced DNA damage. However, in a hMLH1 mutant, only a reduction in the TCR of UV damage was observed. In this study, we examined whether TCR of thymine glycols in Saccharomyces cerecisiae also requires the genes involved in DNA mismatch repair. We found that yeast cells containing mutations in MSH2 were deficient in the removal of thymine glycols from the transcribed strand of the RPB2 gene, while cells with mutations in either MLH1 or PMS1 alone showed near normal levels of TCR of thymine glycols. Interestingly, double mutants in the MLH1 and PMS1 genes were deficient in TCR of thymine glycols. Taken together, these results suggest that these two MutL homologues can act independently of each other, but that they have overlapping roles in TCR. Overall levels of thymine glycol removal were not reduced in the mismatch repair mutants. In contrast to the results with thymine glycols, no defects in TCR of pyrimidine dimers were found in cells with mutations in MSH2, MLH1, PMS1, and MLH1/PMS1.