THE PREVENTION OF REPEAT-ASSOCIATED DELETIONS IN SACCHAROMYCES-CEREVISIAE BY MISMATCH REPAIR DEPENDS ON SIZE AND ORIGIN OF DELETIONS

We have investigated the effects of mismatch repair on 1- to 61-bp del etions in the yeast Saccharomyces cerevisiae. The deletions are likely to involve unpaired loop intermediates resulting from DNA polymerase slippage. The mutator effects of mutations in the DNA polymerase delta (POL3) gene and the recombinational repair RAD52 gene were studied in combination with mismatch repair defects. The pol-3t mutation increas ed up to 1000-fold the rate of extended (7-61 bp) but not of I-bp dele tions. In a rad52 null mutant only the I-bp deletions were increased ( 12-fold). The mismatch repair mutations pms1, msh2 and msh3 did not af fect 31- and 61-bp deletions in the pol3-t but increased the rates of 7- and l-bp deletions. We propose that loops less than or equal to sev en bases generated during replication are subject to mismatch repair b y the PMS1, MSH2, MSH3 system and that it cannot act on loops greater than or equal to 31 bases. In contrast to the pol3-t, the enhancement of l-bp deletions in a rad52 mutant is not altered by a pms1 mutation. Thus, mismatch repair appears to be specific to errors of DNA synthes is generated during semiconservative replication.