3-Methyladenine DNA glycosylase is important for cellular resistance to psoralen interstrand cross-links.

ABSTRACT: DNA interstrand cross-links (ICLs), widely used in chemotherapy, are cytotoxic lesions because they block replication and transcription. Repair of ICLs involves proteins from different repair pathways however the precise mechanism is still not completely understood. Here, we report that the 3-methyladenine DNA glycosylase (Aag), an enzyme that initiates base excision repair at a variety of alkylated bases, is also involved in the repair of ICLs. Aag(-/-) mouse embryonic stem cells were shown to be more sensitive to the cross-linking agent 4,5',8-trimethylpsoralen than wild-type cells, but no more sensitive than wild-type to the psoralen derivative Angelicin that forms only monoadducts. We show that gamma-H2AX foci formation, a marker for double strand breaks that are formed during ICL repa

SUBMITTER: Maor-Shoshani A 

PROVIDER: S-EPMC2583468 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature