RETRACTED: Human SIRT6 promotes DNA end resection through CtIP deacetylation.
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.
Kaidi
Abderrahmane
A
Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Weinert
Brian T
BT
Choudhary
Chunaram
C
Jackson
Stephen P
SP
D000107:Acetylation; D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004247:DNA / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000378:metabolism; D004706:Endodeoxyribonucleases; D042822:Genomic Instability; D006801:Humans; D051379:Mice; D050505:Mutant Proteins / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011995:Recombination, Genetic / Q000187:drug effects; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D004277:DNA, Single-Stranded; D050505:Mutant Proteins; D009687:Nuclear Proteins; D009536:Niacinamide; D004247:DNA; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human; C516592:SIRT6 protein, human; D037761:Sirtuins; D002166:Camptothecin