Increased rates of genomic deletions generated by mutations in the yeast gene encoding DNA polymerase delta or by decreases in the cellular levels ofDNA polymerase delta

In Saccharomyces cerevisiae, POL3 encodes the catalytic subunit of DNA poly merase delta. While yeast POL3 mutant strains that lack the proofreading ex onuclease activity of the polymerase have a strong mutator phenotype, littl e is known regarding the role of other Pol3p domains in mutation avoidance. We identified a number of pol3 mutations in regions outside of the exonucl ease domain that have a mutator phenotype, substantially elevating the freq uency of deletions. These deletions appear to reflect an increased frequenc y of DNA polymerase slippage. In addition, we demonstrate that reduction in the level of wild-type DNA polymerase results in a similar mutator phenoty pe. Lowered levels of DNA polymerase also result in increased sensitivity t o the DNA-damaging agent methyl methane sulfonate, We conclude that both th e quantity and the quality of DNA polymerase delta is important in ensuring genome stability.