PARP1-MGMT complex underpins pathway crosstalk in O⁶-methylguanine repair.

ABSTRACT: DNA lesions induced by alkylating agents are repaired by two canonical mechanisms, base excision repair dependent on poly(ADP) ribose polymerase 1 (PARP1) and the other mediated by O⁶-methylguanine (O⁶meG)-DNA methyltransferase (MGMT) in a single-step catalysis of alkyl-group removal. O⁶meG is the most cytotoxic and mutagenic lesion among the methyl adducts induced by alkylating agents. Although it can accomplish the dealkylation reaction all by itself as a single protein without associating with other repair proteins, evidence is accumulating that MGMT can form complexes with repair proteins and is highly regulated by a variety of post-translational modifications, such as phosphorylation, ubiquitination, and others. Here, we show that PARP1 and MGMT protei

SUBMITTER: Cropper JD 

PROVIDER: S-EPMC9563463 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature