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Journal of Bacteriology, November 1999, p. 6763-6771, Vol. 181, No. 21
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Imbalanced Base Excision Repair Increases Spontaneous Mutation and Alkylation Sensitivity in Escherichia coli

Lauren M. Posnick and Leona D. Samson*

Division of Toxicology, Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115

Received 6 April 1999/Accepted 26 August 1999

Inappropriate expression of 3-methyladenine (3MeA) DNA glycosylases has been shown to have harmful effects on microbial and mammalian cells. To understand the underlying reasons for this phenomenon, we have determined how DNA glycosylase activity and substrate specificity modulate glycosylase effects in Escherichia coli. We compared the effects of two 3MeA DNA glycosylases with very different substrate ranges, namely, the Saccharomyces cerevisiae Mag1 and the E. coli Tag glycosylases. Both glycosylases increased spontaneous mutation, decreased cell viability, and sensitized E. coli to killing by the alkylating agent methyl methanesulfonate. However, Tag had much less harmful effects than Mag1. The difference between the two enzymes' effects may be accounted for by the fact that Tag almost exclusively excises 3MeA lesions, whereas Mag1 excises a broad range of alkylated and other purines. We infer that the DNA lesions responsible for changes in spontaneous mutation, viability, and alkylation sensitivity are abasic sites and secondary lesions resulting from processing abasic sites via the base excision repair pathway.

* Corresponding author. Mailing address: Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115. Phone: (617) 432-1085. Fax: (617) 432-0400. E-mail: lsamson{at}hsph.harvard.edu.

Journal of Bacteriology, November 1999, p. 6763-6771, Vol. 181, No. 21
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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