Increased rates of genomic deletions generated by mutations in the yeast gene encoding DNA polymerase delta or by decreases in the cellular levels of DNA polymerase delta.
In Saccharomyces cerevisiae, POL3 encodes the catalytic subunit of DNA polymerase delta. 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 delta is important in ensuring genome stability.
Kokoska
R J
RJ
Department of Biology, Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280, USA.
Stefanovic
L
L
DeMai
J
J
Petes
T D
TD
D004258:DNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D018900:Dinucleotide Repeats / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D007700:Kinetics; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016296:Mutagenesis / Q000187:drug effects / Q000528:radiation effects; D020125:Mutation, Missense; D010641:Phenotype; D051721:Rad52 DNA Repair and Recombination Protein; D011995:Recombination, Genetic / Q000235:genetics / Q000528:radiation effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics* / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C491232:POL3 protein, S cerevisiae; C497197:RAD52 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D004258:DNA Polymerase III