XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells
XRCC4 in G1 suppresses homologous recombination in S/G2, in G1 checkpoint-defective cells
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DOI：
10.1038/sj.onc.1210075
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发表时间：
2007-04-26
期刊：
影响因子：
8
通讯作者：
Lopez, B. S.
中科院分区：
文献类型：
--
作者：
Saintigny, Y.;Delacote, F.;Lopez, B. S.
非同源末端连接(NHEJ)和同源重组(HR)是DNA双链断裂(DSB)修复的两条相互竞争或协同的途径。NHEJ之前被证明在整个细胞周期中起作用，而HR仅限于S/G2晚期。矛盾的是，我们在这里展示了XRCC4(NHEJ)缺陷导致细胞在G1而不是G2中受到照射时HR的过度刺激。然而，XRCC4缺陷并没有改变对HR(即在S/G2中)严格的细胞周期调控，这表现为：(1)无论XRCC4状态如何，在S/G2晚期都形成了RAD51焦点；(Ii)当细胞被阻断在G1期时，既没有检测到RAD51焦点，也没有检测到电离辐射诱导的HR(基因转换+单链退火)事件。最后，伽马-H_2AX分析和脉冲场凝胶电泳法都表明，照射G1后，在NHEJ缺陷细胞中，一些双链断裂达到了S/G2。综上所述，我们的结果表明，当细胞在G1/S停滞时出现缺陷时，在G1产生的未被XRCC4修复的双链断裂可以被HR处理，但在S/G2晚期可以处理。
Non-homologous end joining (NHEJ) and homologous recombination (HR) are two pathways that can compete or cooperate for DNA double-strand break (DSB) repair. NHEJ was previously shown to act throughout the cell cycle whereas HR is restricted to late S/G2. Paradoxically, we show here that defect in XRCC4 (NHEJ) leads to over-stimulation of HR when cells were irradiated in G1, not in G2. However, XRCC4 defect did not modify the strict cell cycle regulation for HR (i.e. in S/G2) as attested by (i) the formation of Rad51 foci in late S/G2 whatever the XRCC4 status, and (ii) the fact that neither Rad51 foci nor HR (gene conversion plus single-strand annealing) events induced by ionizing radiation were detected when cells were maintained blocked in G1. Finally, both gamma-H2AX analysis and pulse field gel electrophoresis showed that following irradiation in G1, some DSBs reached S/G2 in NHEJ-defective cells. Taken together, our results show that when cells are defective in G1/S arrest, DSB produced in G1 and left unrepaired by XRCC4 can be processed by HR but in late S/G2.