Checkpoint-dependent activation of mutagenic repair in Saccharomyces cerevisiae pol3-01 mutants

The Saccharomyces cerevisiae DNA polymerase delta proofreading exonuclease- defective mutation pol3-01 is known to cause high rates of accumulating mut ations. The pol3-01 mutant was found to have abnormal cell cycle progressio n due to activation of the S phase checkpoint. Inactivation of the S phase checkpoint suppressed both the pol3-01 cell cycle progression defect and mu tator phenotype, indicating that the pol3-01 mutator phenotype was dependen t on the S phase damage checkpoint pathway. Epistasis analysis suggested th at a portion of the pol3-01 mutator phenotype involves members of the RAD6 epistasis group that function in both error-free and error-prone repair. Th ese results indicate that activation of a checkpoint in response to certain types of replicative defects can result in the accumulation of mutations.