Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase.
3-methyladenine (3MeA) DNA glycosylases remove 3MeAs from alkylated DNA to initiate the base excision repair pathway. Here we report the generation of mice deficient in the 3MeA DNA glycosylase encoded by the Aag (Mpg) gene. Alkyladenine DNA glycosylase turns out to be the major DNA glycosylase not only for the cytotoxic 3MeA DNA lesion, but also for the mutagenic 1,N6-ethenoadenine (epsilonA) and hypoxanthine lesions. Aag appears to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung, and the only epsilonA DNA glycosylase in liver, testes, and kidney; another epsilonA DNA glycosylase may be expressed in lung. Although alkyladenine DNA glycosylase has the capacity to remove 8-oxoguanine DNA lesions, it does not appear to be the major glycosylase for 8-oxoguanine repair. Fibroblasts derived from Aag -/- mice are alkylation sensitive, indicating that Aag -/- mice may be similarly sensitive.
Proceedings of the National Academy of Sciences of the United States of America
November 25, 1997
Agency: NCI NIH HHS, Id: 5T32CA09078
Agency: NIEHS NIH HHS, Id: P01-ES03926
Agency: NCI NIH HHS, Id: R01 CA055042
Agency: NCI NIH HHS, Id: R01 CA55042
Mice, Inbred C57BL
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