A MUTATION IN A SACCHAROMYCES-CEREVISIAE GENE (RAD3) REQUIRED FOR NUCLEOTIDE EXCISION-REPAIR AND TRANSCRIPTION INCREASES THE EFFICIENCY OF MISMATCH CORRECTION

RAD3 functions in DNA repair and transcription in Saccharomyces cerevi siae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the pot ential involvement of the Rad3 protein in mismatch correction by compa ring heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutation rate but did not pre vent heteroduplex repair or bias its directionality. Instead, the effi ciency of mismatch correction was enhanced in the rad3-1 strain. This surprising result prompted us to examine expression of yeast mismatch repair genes. We determined that MSH2, but not MLH1, is transcriptiona lly regulated during the cell-cycle like PMS1, and that rad3-1 does no t increase the transcript levels for these genes in log phase cells. T hese observations suggest that the rad3-1 mutation gives rise to an en hanced efficiency of mismatch correction via a process that does not i nvolve transcriptional regulation of mismatch repair. Interestingly, m ismatch repair also was more efficient when error-editing by yeast DNA polymerase delta was eliminated. We discuss our results in relation t o possible mechanisms that may link the rad3-1 mutation to mismatch co rrection efficiency.