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Molecular and Cellular Biology, October 2000, p. 7490-7504, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Robert J. Kokoska, Lela Stefanovic, Jeremy DeMai, and Thomas D. Petes*

Department of Biology, Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599-3280

Received 5 June 2000/Returned for modification 30 June 2000/Accepted 20 July 2000

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.

* Corresponding author. Mailing address: Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599-3280. Phone: (919) 962-1445. Fax: (919) 962-8472. E-mail: tompetes{at}emailunc.edu.

Molecular and Cellular Biology, October 2000, p. 7490-7504, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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