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PMID:20829486
| Citation |
Kaidi, A, Weinert, BT, Choudhary, C and Jackson, SP (2010) Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329:1348-53 |
|---|---|
| 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. |
| Links |
PubMed PMC3276839 Online version:10.1126/science.1192049 |
| Keywords |
Acetylation; Animals; Camptothecin/pharmacology; Carrier Proteins/genetics; Carrier Proteins/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; Nuclear Proteins/metabolism; Protein Binding; Recombination, Genetic/drug effects; Sirtuins/genetics; Sirtuins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
involved_in |
GO:0000724: double-strand break repair via homologous recombination |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0000724: double-strand break repair via homologous recombination |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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