Isolation and characterization of point mutations in mismatch repair genesthat destabilize microsatellites in yeast

The stability of simple repetitive DNA sequences (microsatellites) is a sen sitive indicator of the ability of a cell to repair DNA mismatches. In a ge netic screen for yeast mutants with elevated microsatellite instability, we identified strains containing point mutations in the yeast mismatch repair genes, MSH2, MSH3, MLH1, and PMS1 Some of these mutations conferred phenot ypes significantly different from those of null mutations in these genes. O ne semidominant MSH2 mutation was identified. Finally we showed that strain s heterozygous for null mutations of mismatch repair genes in diploid strai ns in yeast confer subtle defects in the repair of small DNA loops.