Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair
Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair
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人类 SIRT2 和 SIRT3 脱乙酰酶在 DNA 同源重组修复中发挥作用
DOI：
10.1111/gtc.12842
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发表时间：
2021
期刊：
影响因子：
2.1
通讯作者：
Tajima Katsushi
中科院分区：
文献类型：
--
作者：
Yasuda Takeshi;Takizawa Kazuya;Ui Ayako;Hama Michio;Kagawa Wataru;Sugasawa Kaoru;Tajima Katsushi
SIRT 2和SIRT 3蛋白脱乙酰酶维持基因组的完整性和稳定性。然而，它们维持基因组的机制仍不清楚。为了检查SIRT 2和SIRT 3在DSB修复中的作用，在SIRT 2或SIRT 3耗尽的条件下进行了HR、单链退火（SSA）和非同源末端连接（NHEJ）修复的基于I-SceI的GFP报告基因测定。SIRT 2或SIRT 3缺失抑制HR修复与RAD 52缺失相同，但不影响SSA和NHEJ修复。SIRT 2或SIRT 3的缺失干扰了RAD 51向DSB位点的募集，这是RAD 51依赖性HR修复的重要步骤，但不是直接通过RAD 52去乙酰化。SIRT 2或SIRT 3缺失减少了γ H2 AX灶与RPA 1的共定位，因此，它们可能参与启动DSB末端切除，以在HR修复的早期步骤将RAD 51募集到DSB位点。这些结果显示了SIRT 2和SIRT 3在HR中对基因组稳定性的功能的新的潜在机制
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