TY - JOUR
T1 - Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase
AU - Engelward, Bevin P.
AU - Weeda, Geert
AU - Wyatt, Michael D.
AU - Broekhof, José L.M.
AU - De Wit, Jan
AU - Donker, Ingrid
AU - Allan, James M.
AU - Gold, Barry
AU - Hoeijmakers, Jan H.J.
AU - Samson, Leona D.
PY - 1997/11/25
Y1 - 1997/11/25
N2 - 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) gear. 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 (εA) and hypoxanthine lesions. Aag appears to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung, and the only εA DNA glycosylase in liver, testes, and kidney; another εA 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.
AB - 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) gear. 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 (εA) and hypoxanthine lesions. Aag appears to be the only 3MeA and hypoxanthine DNA glycosylase in liver, testes, kidney, and lung, and the only εA DNA glycosylase in liver, testes, and kidney; another εA 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.
UR - http://www.scopus.com/inward/record.url?scp=12644251998&partnerID=8YFLogxK
U2 - 10.1073/pnas.94.24.13087
DO - 10.1073/pnas.94.24.13087
M3 - Article
C2 - 9371804
AN - SCOPUS:12644251998
SN - 0027-8424
VL - 94
SP - 13087
EP - 13092
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -