First Author | Kaidi A | Year | 2010 |
Journal | Science | Volume | 329 |
Issue | 5997 | Pages | 1348-53 |
PubMed ID | 20829486 | Mgi Jnum | J:163815 |
Mgi Id | MGI:4830004 | Doi | 10.1126/science.1192049 |
Citation | Kaidi A, et al. (2010) Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329(5997):1348-53 |
abstractText | SIRT6 belongs to the sirtuin family of protein lysine deacetylases, which regulate aging and genome stability. We found that human SIRT6 has a role in promoting DNA end resection, a crucial step in DNA double-strand break (DSB) repair by homologous recombination. SIRT6 depletion impaired the accumulation of replication protein A and single-stranded DNA at DNA damage sites, reduced rates of homologous recombination, and sensitized cells to DSB-inducing agents. We identified the DSB resection protein CtIP [C-terminal binding protein (CtBP) interacting protein] as a SIRT6 interaction partner and showed that SIRT6-dependent CtIP deacetylation promotes resection. A nonacetylatable CtIP mutant alleviated the effect of SIRT6 depletion on resection, thus identifying CtIP as a key substrate by which SIRT6 facilitates DSB processing and homologous recombination. These findings further clarify how SIRT6 promotes genome stability. |