Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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}crchul.ulaval.ca

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882