title: 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.
authors.affiliation: Department of Chemistry, Johns Hopkins University , 3400 N. Charles St., Baltimore, Maryland 21218, United States.
authors.forename: Marisa L
authors.initials: ML
authors.lastname: Taverna Porro
authors.forename: Marc M
authors.initials: MM
authors.lastname: Greenberg
mesh_terms: D053903:DNA Breaks, Double-Stranded; D053837:DNA Cleavage; D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry*; D008958:Models, Molecular
chemical_list: D005609:Free Radicals; D006859:Hydrogen