Engelward B P, Weeda G, Wyatt M D, Broekhof J L, de Wit J, Donker I, Allan J M, Gold B, Hoeijmakers J H, Samson L D
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13087-92. doi: 10.1073/pnas.94.24.13087.
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.
3-甲基腺嘌呤（3MeA）DNA糖基化酶从烷基化DNA中去除3MeA，以启动碱基切除修复途径。在此，我们报告了通过Aag（Mpg）基因编码的3MeA DNA糖基化酶缺陷型小鼠的产生。烷基腺嘌呤DNA糖基化酶不仅是细胞毒性3MeA DNA损伤的主要DNA糖基化酶，也是诱变1,N6-乙烯腺嘌呤（εA）和次黄嘌呤损伤的主要DNA糖基化酶。Aag似乎是肝脏、睾丸、肾脏和肺中唯一的3MeA和次黄嘌呤DNA糖基化酶，也是肝脏、睾丸和肾脏中唯一的εA DNA糖基化酶；另一种εA DNA糖基化酶可能在肺中表达。尽管烷基腺嘌呤DNA糖基化酶有能力去除8-氧鸟嘌呤DNA损伤，但它似乎不是8-氧鸟嘌呤修复的主要糖基化酶。来自Aag -/-小鼠的成纤维细胞对烷基化敏感，表明Aag -/-小鼠可能同样敏感。
