DNA Double Strand Cleavage via Interstrand Hydrogen Atom Abstraction

MARISA L. TAVERNA PORRO; MARC M. GREENBERG

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Lugar: Washington; Año: 2013 vol. 135 p. 16368 - 16371

0002-7863

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.