Increased Rates of Genomic Deletions Generated by Mutations in the Yeast Gene Encoding DNA Polymerase δ or by Decreases in the Cellular Levels of DNA Polymerase δ

In Saccharomyces cerevisiae, POL3 encodes the catalytic subunit of DNA polymerase δ. While yeast POL3 mutant strains that lack the proofreading exonuclease activity of the polymerase have a strong mutator phenotype, little is known regarding the role of other Pol3p domains in mutation avoidance. We identified a number of pol3 mutations in regions outside of the exonuclease domain that have a mutator phenotype, substantially elevating the frequency of deletions. These deletions appear to reflect an increased frequency of DNA polymerase slippage. In addition, we demonstrate that reduction in the level of wild-type DNA polymerase results in a similar mutator phenotype. Lowered levels of DNA polymerase also result in increased sensitivity to the DNA-damaging agent methyl methane sulfonate. We conclude that both the quantity and the quality of DNA polymerase δ is important in ensuring genome stability.