Publication Date:
2010-09-11
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276839/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276839/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaidi, Abderrahmane -- Weinert, Brian T -- Choudhary, Chunaram -- Jackson, Stephen P -- 11224/Cancer Research UK/United Kingdom -- A5290/Cancer Research UK/United Kingdom -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Sep 10;329(5997):1348-53. doi: 10.1126/science.1192049.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20829486" target="_blank"〉PubMed〈/a〉
Keywords:
Acetylation
;
Animals
;
Camptothecin/pharmacology
;
Carrier Proteins/genetics/*metabolism
;
Cell Cycle
;
Cell Line
;
Cell Line, Tumor
;
Cell Proliferation
;
DNA/*metabolism
;
*DNA Breaks, Double-Stranded
;
*DNA Repair
;
DNA, Single-Stranded/metabolism
;
Genomic Instability
;
Humans
;
Mice
;
Mutant Proteins/metabolism
;
Niacinamide/pharmacology
;
Nuclear Proteins/genetics/*metabolism
;
Protein Binding
;
Recombination, Genetic/drug effects
;
Sirtuins/genetics/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
