Parp1 activation in mouse embryonic fibroblasts promotes Pol beta-dependent cellular hypersensitivity to alkylation damage.

ABSTRACT: Alkylating agents induce cell death in wild-type (WT) mouse embryonic fibroblasts (MEFs) by multiple mechanisms, including apoptosis, autophagy and necrosis. DNA polymerase beta (Pol beta) knockout (KO) MEFs are hypersensitive to the cytotoxic effect of alkylating agents, as compared to WT MEFs. To test the hypothesis that Parp1 is preferentially activated by methyl methanesulfonate (MMS) exposure of Pol beta KO MEFs, we have examined the relationship between Pol beta expression, Parp1 activation and cell survival following MMS exposure in a series of WT and Pol beta deficient MEF cell lines. Consistent with our hypothesis, we observed elevated Parp1 activation in Pol beta KO MEFs as compared to matched WT MEFs. Both the MMS-induced activation of Parp1 and the MMS-induced cytotoxicity of P

SUBMITTER: Jelezcova E 

PROVIDER: S-EPMC2834876 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature