Sirtuin 6 and DNA Repair

Science Signaling  21 Jun 2011:
Vol. 4, Issue 178, pp. ec177
DOI: 10.1126/scisignal.4178ec177

The mammalian silent chromatin regulator family of proteins (sirtuins, or SIRT) are involved in stress response and genome maintenance pathways. They have dual enzymic activities, functioning as both deacetylases and mono-ADP-ribosyltransferases. Mao et al. show that SIRT6 functions in double-strand-break (DSB) DNA repair, through the homologous recombination and nonhomologous end joining repair pathways. The repair activity is highly stimulated under conditions of stress, when SIRT6 is rapidly recruited to sites of DNA damage. SIRT6 then associates with, and mono-ADP-ribosylates, the poly-ADP ribose polymerase 1 (PARP1), thereby activating PARP1 to poly-ADP-ribosylate other break-associated proteins, facilitating recruitment of additional DNA repair factors. Because PARP1 is involved in both base excision repair and DSB repair, SIRT6 integrates DNA repair and stress signaling pathways.

Z. Mao, C. Hine, X. Tian, M. Van Meter, M. Au, A. Vaidya, A. Seluanov, V. Gorbunova, SIRT6 promotes DNA repair under stress by activating PARP1. Science 332, 1443–1446 (2011). [Abstract] [Full Text]