Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair
- 23 February 2021
- journal article
- research article
- Published by Wiley in Genes to Cells
- Vol. 26 (5), 328-335
- https://doi.org/10.1111/gtc.12842
Abstract
SIRT2 and SIRT3 protein deacetylases maintain genome integrity and stability. However, their mechanisms for maintaining the genome remain unclear. To examine the roles of SIRT2 and SIRT3 in DSB repair, I‐SceI‐based GFP reporter assays for HR, single‐strand annealing (SSA) and nonhomologous end joining (NHEJ) repair were performed under SIRT2‐ or SIRT3‐depleted conditions. SIRT2 or SIRT3 depletion inhibited HR repair equally to RAD52 depletion, but did not affect SSA and NHEJ repairs. SIRT2 or SIRT3 depletion disturbed the recruitment of RAD51 to DSB sites, an essential step for RAD51‐dependent HR repair, but not directly through RAD52 deacetylation. SIRT2 or SIRT3 depletion decreased the colocalization of γH2AX foci with RPA1, and thus, they might be involved in initiating DSB end resection for the recruitment of RAD51 to DSB sites at an early step in HR repair. These results show the novel underlying mechanism of the SIRT2 and SIRT3 functions in HR for genome stabilityKeywords
Funding Information
- Japan Society for the Promotion of Science (20K12177, 26281026)
This publication has 46 references indexed in Scilit:
- Interaction of Sirt3 with OGG1 contributes to repair of mitochondrial DNA and protects from apoptotic cell death under oxidative stressCell Death & Disease, 2013
- SIRT2 Maintains Genome Integrity and Suppresses Tumorigenesis through Regulating APC/C ActivityCancer Cell, 2011
- Who's who in human recombination: BRCA2 and RAD52Proceedings of the National Academy of Sciences of the United States of America, 2010
- Sirt3-Mediated Deacetylation of Evolutionarily Conserved Lysine 122 Regulates MnSOD Activity in Response to StressMolecular Cell, 2010
- Rad52 inactivation is synthetically lethal with BRCA2 deficiencyProceedings of the National Academy of Sciences of the United States of America, 2010
- Acetylation of Dna2 Endonuclease/Helicase and Flap Endonuclease 1 by p300 Promotes DNA Stability by Creating Long Flap IntermediatesOnline Journal of Public Health Informatics, 2010
- SIRT1 deacetylates APE1 and regulates cellular base excision repairNucleic Acids Research, 2009
- Rad52 promotes second-end DNA capture in double-stranded break repair to form complement-stabilized joint moleculesProceedings of the National Academy of Sciences of the United States of America, 2009
- Rad51 Protein Controls Rad52-mediated DNA AnnealingOnline Journal of Public Health Informatics, 2008
- SIRT1 Regulates the Function of the Nijmegen Breakage Syndrome ProteinMolecular Cell, 2007