Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM-/- and c-Abl-/- cells
Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM-/- and c-Abl-/- cells
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DOI：
10.1016/s0027-5107(03)00009-5
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发表时间：
2003-04-09
影响因子：
2.3
通讯作者：
Lee, EYHP
中科院分区：
文献类型：
--
作者：
Yuan, SSF;Chang, HL;Lee, EYHP
在真核生物中，DNA 双链断裂 (DSB) 可以通过非同源末端连接 (NHEJ) 或同源重组 (HR) 途径修复。 Rad50 蛋白是 Rad50/NBS1/Mre11 核酸酶复合物的组成部分，在 NHEJ 和 DNA DSB 重组修复中发挥作用。另一方面，Rad51 蛋白是细菌 RecA 的同源物，也是 Rad52 上位性组的成员，在重组修复途径中发挥着至关重要的作用。我们分析了细胞周期进程和遗传背景对电离辐射 (IR) 诱导的 Rad51 和 Rad50 修复灶形成的影响。在此，我们证明了 IR 诱导的 Rad51（而非 Rad50）核灶形成具有细胞周期依赖性。此外，IR诱导的Rad51焦点形成在AT和c-Abl(-/-)细胞中是有缺陷的，但在野生型或NBS细胞中则没有。 IR后，在AT细胞中观察到含Rad51焦点的细胞核形成减少且延迟，而在c-Abl(-/-)细胞中观察到含Rad(51)焦点的细胞核形成减少但不延迟。总之，有效且迅速的 IR 诱导的 Rad51 焦点形成是细胞周期调节的，并且需要 ATM 和 c-Abl。 (C) 2003 Elsevier Science B.V. 保留所有权利。
In eukaryotes, DNA double-strand breaks (DSBs) can be repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways. Rad50 protein is a component of the Rad50/NBS1/Mre11 nuclease complex that functions in both the NHEJ and recombinational repair of DNA DSBs. On the other hand, Rad51 protein, a homolog of bacterial RecA and a member of the Rad52 epistasis group, plays a crucial role exclusively in the recombinational repair pathway. We analyzed the effects of cell cycle progression and genetic background on the ionizing radiation (IR)-induced Rad51 and Rad50 repair focus formation. Herein, we demonstrated that IR-induced Rad51, but not Rad50, nuclear focus formation was cell cycle-dependent. Furthermore, IR-induced Rad51 focus formation was defective in AT and c-Abl(-/-)cells, but not wild type or NBS cells. A decreased and delayed formation of Rad51 foci-containing nuclei was observed in AT cells upon IR, whereas in c-Abl(-/-) cells a decreased but not delayed formation of Rad(51) foci-containing nuclei was observed. In conclusion, effective and prompt IR-induced Rad51 focus formation is cell cycle-regulated and requires both ATM and c-Abl. (C) 2003 Elsevier Science B.V. All rights reserved.