人类 SIRT2 和 SIRT3 去乙酰化酶在 DNA 同源重组修复中发挥作用。
Human SIRT2 and SIRT3 deacetylases function in DNA homologous recombinational repair.
机构信息
National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Sciences and Technology (QST), Chiba, Japan.
Department of Molecular Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
出版信息
Genes Cells. 2021 May;26(5):328-335. doi: 10.1111/gtc.12842. Epub 2021 Mar 18.
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.
SIRT2 和 SIRT3 蛋白去乙酰化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尚不清楚。为了研究 SIRT2 和 SIRT3 在 DSB 修复中的作用，在 SIRT2 或 SIRT3 耗尽的条件下，利用基于 I-SceI 的 GFP 报告基因检测 HR、单链退火 (SSA) 和非同源末端连接 (NHEJ) 修复。SIRT2 或 SIRT3 的耗竭与 RAD52 的耗竭同样抑制 HR 修复，但不影响 SSA 和 NHEJ 修复。SIRT2 或 SIRT3 的耗竭干扰了 RAD51 到 DSB 位点的募集，这是 RAD51 依赖的 HR 修复的一个必要步骤，但不是通过 RAD52 的去乙酰化直接进行的。SIRT2 或 SIRT3 的耗竭减少了 γH2AX 焦点与 RPA1 的共定位，因此，它们可能参与启动 DSB 末端切除，以便在 HR 修复的早期步骤中将 RAD51 募集到 DSB 位点。这些结果表明了 SIRT2 和 SIRT3 在 HR 中维持基因组稳定性的功能的新的潜在机制。
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