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Science 336 (6082): 678-679

Copyright © 2012 by the American Association for the Advancement of Science

PARP-1 Activation—Bringing the Pieces Together

Jean-Philippe Gagné, Michèle Rouleau, Guy G. Poirier

The repair of DNA strand breaks is crucial for cell survival. In higher eukaryotes, cellular responses to DNA strand breaks are coordinated by a process called poly(ADP-ribosyl)ation (where ADP is adenosine diphosphate). This highly dynamic process begins with the hydrolysis of NAD+ (nicotinamide adenine dinucleotide) by poly(ADP-ribose) polymerases (PARPs), resulting in the polymerization of ADP-ribose moieties onto a substrate protein. The most active PARP in DNA damage recognition, PARP-1, is highly stimulated by single- and double-strand breaks (1). Because it is a clinically important molecular target in the treatment of several cancers, including breast and ovarian cancers (2), understanding how PARP-1 is activated after binding DNA strand breaks is an ongoing challenge. On page 728 of this issue, Langelier et al. (3) report key structural information about PARP-1 domain organization around a DNA double-strand break (DSB) that explains this activation.

CHUQ Research Center-CHUL, Cancer Research Unit, Laval University, Québec, Canada.

E-mail: guy.poirier{at}

Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
J. Murai, S.-y. N. Huang, B. B. Das, A. Renaud, Y. Zhang, J. H. Doroshow, J. Ji, S. Takeda, and Y. Pommier (2012)
Cancer Res. 72, 5588-5599
   Abstract »    Full Text »    PDF »
Alternative Modes of Binding of Poly(ADP-ribose) Polymerase 1 to Free DNA and Nucleosomes.
N. J. Clark, M. Kramer, U. M. Muthurajan, and K. Luger (2012)
J. Biol. Chem. 287, 32430-32439
   Abstract »    Full Text »    PDF »

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