Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase

BP Engelward, G Weeda, MD Wyatt… - Proceedings of the …, 1997 - National Acad Sciences
BP Engelward, G Weeda, MD Wyatt, JLM Broekhof, J De Wit, I Donker, JM Allan, B Gold…
Proceedings of the National Academy of Sciences, 1997National Acad Sciences
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, N 6-ethenoadenine (ɛA) and hypoxanthine lesions. Aag appears
to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung …
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 (ɛA) and hypoxanthine lesions. Aag appears to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung, and the only ɛA DNA glycosylase in liver, testes, and kidney; another ɛA 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.
National Acad Sciences