DNA double strand cleavage via interstrand hydrogen atom abstraction.

ABSTRACT: Double strand breaks (DSBs) are the most deleterious form of DNA damage. Natural products that produce them are potent cytotoxic agents. Designing molecules that produce DSBs via a single chemical event is challenging. We determined that formation of a C4'-nucleotide radical in duplex DNA under aerobic conditions gives rise to a DSB. The original radical yields a strand break containing a peroxyl radical, which initiates opposite strand cleavage via C4'-hydrogen atom abstraction. This mechanism provides the impetus to design DNA damaging agents that produce DSBs by abstracting a single hydrogen atom from the biopolymer.

SUBMITTER: Taverna Porro ML 

PROVIDER: S-EPMC3852885 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature