Nucleic Acids Research, 2000, Vol. 28, No. 16 3040-3046
© 2000 Oxford University Press
DNA polymerase ß is required for efficient DNA strand break repair induced by methyl methanesulfonate but not by hydrogen peroxide
Laboratory of Comparative Toxicology and Ecotoxicology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
The most frequent DNA lesions in mammalian genomes are removed by the base excision repair (BER) via multiple pathways that involve the replacement of one or more nucleotides at the lesion site. The biological consequences of a BER defect are at present largely unknown. We report here that mouse cells defective in the main BER DNA polymerase ß (Pol ß) display a decreased rate of DNA single-strand breaks (ssb) rejoining after methyl methanesulfonate damage when compared with wild-type cells. In contrast, Pol ß seems to be dispensable for hydrogen peroxide-induced DNA ssb repair, which is equally efficient in normal and defective cells. By using an in vitro repair assay on single abasic site-containing circular duplex molecules, we show that the long-patch BER is the predominant repair route in Pol ß-null cell extract. Our results strongly suggest that the Pol ß-mediated single nucleotide BER is the favorite pathway for repair of N-methylpurines while oxidation-induced ssb, likely arising from oxidized abasic sites, are the substrate for long-patch BER.
* To whom correspondence should be addressed. Tel: +39 06 4990 2580; Fax: +39 06 4990 2355; Email: dogliott@iss.itThe authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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