title: RETRACTED: Human SIRT6 promotes DNA end resection through CtIP deacetylation.
abstract: 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.
authors.affiliation: Gurdon Institute and Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Abderrahmane
authors.initials: A
authors.lastname: Kaidi
authors.forename: Brian T
authors.initials: BT
authors.lastname: Weinert
authors.forename: Chunaram
authors.initials: C
authors.lastname: Choudhary
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: 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*
chemical_list: 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