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Molecular and Cellular Biology, April 1999, p. 2929-2935, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Overlapping Specificities of Base Excision Repair, Nucleotide Excision Repair, Recombination, and Translesion Synthesis Pathways for DNA Base Damage in Saccharomyces cerevisiae

Rebecca L. Swanson,1,2 Natalie J. Morey,3,4 Paul W. Doetsch,1,5,* and Sue Jinks-Robertson3,*

Departments of Biochemistry1 and Biology,3 Graduate Program in Nutrition and Health Sciences,2 Graduate Program in Genetics and Molecular Biology,4 and Division of Cancer Biology, Department of Radiation Oncology,5 Emory University School of Medicine, Atlanta, Georgia 30322

Received 13 November 1998/Returned for modification 18 December 1998/Accepted 4 January 1999

The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coli endonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of damaged pyrimidines (H. J. You, R. L. Swanson, and P. W. Doetsch, Biochemistry 37:6033-6040, 1998). The biological relevance of the N-glycosylase-associated AP lyase activity in the repair of abasic sites is not well understood, and the majority of AP sites in vivo are thought to be processed by Apn1p, the major AP endonuclease in yeast. We have found that yeast cells simultaneously lacking Ntg1p, Ntg2p, and Apn1p are hyperrecombinogenic (hyper-rec) and exhibit a mutator phenotype but are not sensitive to the oxidizing agents H2O2 and menadione. The additional disruption of the RAD52 gene in the ntg1 ntg2 apn1 triple mutant confers a high degree of sensitivity to these agents. The hyper-rec and mutator phenotypes of the ntg1 ntg2 apn1 triple mutant are further enhanced by the elimination of the nucleotide excision repair pathway. In addition, removal of either the lesion bypass (Rev3p-dependent) or recombination (Rad52p-dependent) pathway specifically enhances the hyper-rec or mutator phenotype, respectively. These data suggest that multiple pathways with overlapping specificities are involved in the removal of, or tolerance to, spontaneous DNA damage in S. cerevisiae. In addition, the fact that these responses to induced and spontaneous damage depend upon the simultaneous loss of Ntg1p, Ntg2p, and Apn1p suggests a physiological role for the AP lyase activity of Ntg1p and Ntg2p in vivo.

* Corresponding author. Mailing address for Paul W. Doetsch: Department of Biochemistry, Rollins Research Center, 1510 Clifton Rd., Emory University, Atlanta, GA 30322. Phone: (404) 727-0409. Fax: (404) 727-3954. E-mail: medpwd{at}emory.edu. Mailing address for Sue Jinks-Robertson: Department of Biology, Rollins Research Center, 1510 Clifton Rd., Emory University, Atlanta, GA 30322. Phone: (404) 727-6312. Fax: (404) 727-2880. E-mail: jinks{at}biology.emory.edu.

Molecular and Cellular Biology, April 1999, p. 2929-2935, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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