Analysis of yeast pms1, msh2, and mlh1 mutators points to differences in mismatch correction efficiencies between prokaryotic and eukaryotic cells

Genetic stability relies in part on the efficiency with which post-replicat ive mismatch repair (MMR) detects and corrects DNA replication errors. In E scherichia coli, endogenous transition mispairs and insertion/deletion (ID) heterologies are corrected with similar efficiencies - but much more effic iently than transversion mispairs - as revealed by mutation rate increases in MMR mutants. To assess the relative efficiencies with which these mismat ches are corrected in the yeast Saccharomyces cerevisiae, we examined repai r of defined mismatches on heteroduplex plasmids and compared the spectra f or >1000 spontaneous SUP4-o mutations arising in isogenic wild-type or MMR- deficient (pms1, mlh1, msh2) strains. Heteroduplexes containing G/T mispair s or ID heterologies were corrected more efficiently than those containing transversion mismatches. However, the rates of single base-pair insertion/d eletion were increased much more (82-fold or 34-fold, respectively) on aver age than the rate of base pair substitutions (4.4-fold), with the rates for total transitions and transversions increasing to similar extents. Thus, t he relative efficiencies with which mismatches formed during DNA replicatio n are repaired appear to differ in prokaryotic and eukaryotic cells. In add ition, our results indicate that in yeast, and probably other eukaryotes, t hese efficiencies may not mirror those obtained from an analysis of heterod uplex correction.