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J Bacteriol, May 1998, p. 2292-2297, Vol. 180, No. 9
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

The Pol beta -14 Dominant Negative Rat DNA Polymerase beta  Mutator Mutant Commits Errors during the Gap-Filling Step of Base Excision Repair in Saccharomyces cerevisiaedagger

Caroline A. Clairmont1,Dagger and Joann B. Sweasy1,2,*

Departments of Therapeutic Radiology 1 and Genetics, 2 Yale University School of Medicine, New Haven, Connecticut 06520

Received 30 October 1997/Accepted 23 February 1998

We demonstrated recently that dominant negative mutants of rat DNA polymerase beta  (Pol beta ) interfere with repair of alkylation damage in Saccharomyces cerevisiae. To identify the alkylation repair pathway that is disrupted by the Pol beta  dominant negative mutants, we studied the epistatic relationship of the dominant negative Pol beta  mutants to genes known to be involved in repair of DNA alkylation damage in S. cerevisiae. We demonstrate that the rat Pol beta  mutants interfere with the base excision repair pathway in S. cerevisiae. In addition, expression of one of the Pol beta  dominant negative mutants, Pol beta -14, increases the spontaneous mutation rate of S. cerevisiae whereas expression of another Pol beta  dominant negative mutant, Pol beta -TR, does not. Expression of the Pol beta -14 mutant in cells lacking APN1 activity does not result in an increase in the spontaneous mutation rate. These results suggest that gaps are required for mutagenesis to occur in the presence of Pol beta -14 but that it is not merely the presence of a gap that results in mutagenesis. Our results suggest that mutagenesis can occur during the gap-filling step of base excision repair in vivo.

* Corresponding author. Mailing address: Dept. of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208040, New Haven, CT 06520-8040. Phone: (203) 737-2626. Fax: (203) 785-6309. E-mail: Joann.Sweasy{at}Yale.edu.

dagger Dedicated to the memory of Franklin Hutchinson.

Dagger Present address: Vion Pharmaceuticals, Inc., New Haven, CT 06511.

J Bacteriol, May 1998, p. 2292-2297, Vol. 180, No. 9
0021-9193/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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