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Science 332 (6036): 1443-1446

Copyright © 2011 by the American Association for the Advancement of Science

SIRT6 Promotes DNA Repair Under Stress by Activating PARP1

Zhiyong Mao, Christopher Hine, Xiao Tian, Michael Van Meter, Matthew Au, Amita Vaidya, Andrei Seluanov,* Vera Gorbunova*

Abstract: Sirtuin 6 (SIRT6) is a mammalian homolog of the yeast Sir2 deacetylase. Mice deficient for SIRT6 exhibit genome instability. Here, we show that in mammalian cells subjected to oxidative stress SIRT6 is recruited to the sites of DNA double-strand breaks (DSBs) and stimulates DSB repair, through both nonhomologous end joining and homologous recombination. Our results indicate that SIRT6 physically associates with poly[adenosine diphosphate (ADP)–ribose] polymerase 1 (PARP1) and mono-ADP-ribosylates PARP1 on lysine residue 521, thereby stimulating PARP1 poly-ADP-ribosylase activity and enhancing DSB repair under oxidative stress.

Department of Biology, University of Rochester, Rochester, NY 14627, USA.

* To whom correspondence should be addressed. E-mail: vera.gorbunova{at}rochester.edu (V.G.); andrei.seluanov{at}rochester.edu (A.S.)

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