The spatial organization of non-homologous end joining: from bridging to end joining.
The spatial organization of non-homologous end joining: from bridging to end joining.
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DOI：
10.1016/j.dnarep.2014.02.010
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发表时间：
2014-05
期刊：
影响因子：
3.8
通讯作者：
Blundell, Tom L.
中科院分区：
文献类型：
--
作者：
Ochi, Takashi;Wu, Qian;Blundell, Tom L.
NHEJ的结构分析揭示了DNA双链断裂修复的机制。Artemis与LigIV和DNA-PK的复合物定义了时空关系。Artemis， LigIV和XLF的致病突变用3D结构解释。非同源末端连接（Non-homologous end joining， NHEJ）可以修复DNA损伤引起的DNA双链断裂，也可以修复免疫系统中免疫球蛋白和T细胞受体产生过程中V(D)J重组中发生的DNA双链断裂。在NHEJ中，DNA- pkcs与Ku异源二聚体在双链断裂的DNA末端组装，以便将断裂的末端连接在一起，并组装其他蛋白质，包括DNA修复所需的DNA连接酶IV （LigIV）。在这里，我们重点研究了LigIV与XRCC4、XLF、Artemis和参与NHEJ桥接和末端连接步骤的DNA相互作用的结构方面。我们首先讨论了XLF的作用，它与Ku相互作用并与XRCC4形成异质丝；这可能会形成一个连接DNA末端的支架。然后，我们回顾了XRCC4与LigIV明确定义的相互作用，并讨论了这种复合物中断细丝形成的可能性，从而将连接酶定位在靠近断裂端的正确位置。我们还描述了LigIV与Artemis的相互作用，Artemis是一种核酸酶，为结扎准备末端，也与DNA-PK相互作用。最后，我们回顾了孟德尔突变对这些多蛋白组合的可能影响及其对遗传疾病形式的影响。
Structural analyses of NHEJ suggest mechanisms of DNA double-strand break repair. Complexes of Artemis with LigIV and DNA-PK define spatiotemporal relationships. Disease-causing mutations in Artemis, LigIV and XLF are explained by 3D structure. Non-homologous end joining (NHEJ) repairs DNA double-strand breaks generated by DNA damage and also those occurring in V(D)J recombination in immunoglobulin and T cell receptor production in the immune system. In NHEJ DNA-PKcs assembles with Ku heterodimer on the DNA ends at double-strand breaks, in order to bring the broken ends together and to assemble other proteins, including DNA ligase IV (LigIV), required for DNA repair. Here we focus on structural aspects of the interactions of LigIV with XRCC4, XLF, Artemis and DNA involved in the bridging and end-joining steps of NHEJ. We begin with a discussion of the role of XLF, which interacts with Ku and forms a hetero-filament with XRCC4; this likely forms a scaffold bridging the DNA ends. We then review the well-defined interaction of XRCC4 with LigIV, and discuss the possibility of this complex interrupting the filament formation, so positioning the ligase at the correct positions close to the broken ends. We also describe the interactions of LigIV with Artemis, the nuclease that prepares the ends for ligation and also interacts with DNA-PK. Lastly we review the likely affects of Mendelian mutations on these multiprotein assemblies and their impacts on the form of inherited disease.
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影响因子：
5.7
作者：
Chen, L;Morio, T;Mizutani, S
通讯作者：
Mizutani, S
DOI：
10.1016/s0921-8777(98)00063-9
发表时间：
1999-01-26
期刊：
MUTATION RESEARCH-DNA REPAIR
影响因子：
--
作者：
Bryans, M;Valenzano, MC;Stamato, TD
通讯作者：
Stamato, TD
影响因子：
3.8
作者：
Chen, Xi;Ballin, Jeff D.;Wilson, Gerald M.
通讯作者：
Wilson, Gerald M.
影响因子：
2.9
作者：
Cotner-Gohara, Elizabeth;Kim, Ln-Kwon;Hammel, Michal;Tainer, John A.;Tomkinson, Alan E.;Ellenberger, Tom
通讯作者：
Ellenberger, Tom
影响因子：
11.4
作者：
Boskovic, J;Rivera-Calzada, A;Llorca, O
通讯作者：
Llorca, O