Human SIRT6 promotes DNA end resection through CtIP deacetylation

Abderrahmane Kaidi, Brian T Weinert, Chunaram Choudhary, Stephen P Jackson

Research output: Contribution to journalArticle (Academic Journal)peer-review

282 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1348-1353
Number of pages6
JournalScience
Volume329
Issue number5997
DOIs
Publication statusPublished - 10 Sep 2010

Keywords

  • Acetylation
  • Animals
  • Camptothecin
  • Carrier Proteins
  • Cell Cycle
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • DNA, Single-Stranded
  • Genomic Instability
  • Humans
  • Mice
  • Mutant Proteins
  • Niacinamide
  • Nuclear Proteins
  • Protein Binding
  • Recombination, Genetic
  • Sirtuins

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