Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair,Genes to Cells

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Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair
Genes to Cells ( IF 1.3 ) Pub Date : 2021-02-23 , DOI: 10.1111/gtc.12842
Takeshi Yasuda ₁ , Kazuya Takizawa ₁ , Ayako Ui _{2,

3} , Michio Hama ₁ , Wataru Kagawa ₄ , Kaoru Sugasawa ₅ , Katsushi Tajima ₁

Affiliation

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 stability

中文翻译：

人SIRT2和SIRT3脱乙酰酶在DNA同源重组修复中的功能

SIRT2和SIRT3蛋白脱乙酰基酶保持基因组的完整性和稳定性。但是，它们维持基因组的机制仍不清楚。为了检查SIRT2和SIRT3在DSB修复中的作用，在SIRT2或SIRT3耗尽的条件下，进行了基于I-SceI的HR GFP报告基因检测，单链退火（SSA）和非同源末端连接（NHEJ）修复。SIRT2或SIRT3耗竭与RAD52耗竭同样抑制HR修复，但不影响SSA和NHEJ修复。SIRT2或SIRT3耗竭干扰了RAD51向DSB部位的募集，这是RAD51依赖的HR修复的重要步骤，但不是直接通过RAD52脱乙酰作用。SIRT2或SIRT3耗竭降低了γH2AX病灶与RPA1的共定位，因此，他们可能会参与启动DSB末端切除术，以便在HR修复的早期将RAD51募集到DSB部位。这些结果表明，SIRT2和SIRT3在HR中为基因组稳定性提供新的潜在机制

更新日期：2021-02-23

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