RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation.
RAD51C facilitates checkpoint signaling by promoting CHK2 phosphorylation.
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DOI：
10.1083/jcb.200811079
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发表时间：
2009-05-18
期刊：
影响因子：
--
通讯作者：
Tarsounas M
中科院分区：
文献类型：
--
作者：
Badie S;Liao C;Thanasoula M;Barber P;Hill MA;Tarsounas M
RAD51旁系同源物在DNA修复的同源重组（HR）途径中起作用。人RAD51 C（hRAD51 C）参与分支迁移和霍利迪连接分辨率，因此在DNA修复过程的后期加工HR中间体是重要的。在DNA修复过程中，也存在早期参与RAD 51的证据，但其在此背景下的功能尚不清楚。在这项研究中，我们证明，RAD51C积累在DNA损伤位点伴随着RAD51重组酶，并保留后RAD51拆卸，这是一致的早期和晚期功能RAD51C。RAD51C的募集依赖于共济失调毛细血管扩张突变、NBS1和复制蛋白A，表明它在DNA末端切除后但在RAD51组装前发挥作用。此外，我们发现RAD51C是激活检查点激酶CHK2和细胞周期阻滞所必需的，以响应DNA损伤。这表明hRAD 51 C除了参与HR机制之外，还通过转导DNA损伤信号来保护基因组完整性。
The RAD51 paralogues act in the homologous recombination (HR) pathway of DNA repair. Human RAD51C (hRAD51C) participates in branch migration and Holliday junction resolution and thus is important for processing HR intermediates late in the DNA repair process. Evidence for early involvement of RAD51 during DNA repair also exists, but its function in this context is not understood. In this study, we demonstrate that RAD51C accumulates at DNA damage sites concomitantly with the RAD51 recombinase and is retained after RAD51 disassembly, which is consistent with both an early and a late function for RAD51C. RAD51C recruitment depends on ataxia telangiectasia mutated, NBS1, and replication protein A, indicating it functions after DNA end resection but before RAD51 assembly. Furthermore, we find that RAD51C is required for activation of the checkpoint kinase CHK2 and cell cycle arrest in response to DNA damage. This suggests that hRAD51C contributes to the protection of genome integrity by transducing DNA damage signals in addition to engaging the HR machinery.
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DOI：
10.1083/jcb.200510130
发表时间：
2006-04-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bekker-Jensen S;Lukas C;Kitagawa R;Melander F;Kastan MB;Bartek J;Lukas J
通讯作者：
Lukas J
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
3.5
作者：
Barber, PR;Vojnovic, B;Joiner, MC
通讯作者：
Joiner, MC
影响因子：
4
作者：
Bennett, BT;Knight, KL
通讯作者：
Knight, KL
影响因子：
16
作者：
Davies, AA;Masson, JY;West, SC
通讯作者：
West, SC