The role of homologous recombination in radiation-induced double-strand break repair
The role of homologous recombination in radiation-induced double-strand break repair
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DOI：
10.1016/j.radonc.2011.06.019
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发表时间：
2011-10-01
影响因子：
5.7
通讯作者：
Loebrich, Markus
中科院分区：
文献类型：
--
作者：
Jeggo, Penny A.;Geuting, Verena;Loebrich, Markus
DNA双链断裂（DSB）是电离辐射（IR）引起的最具生物学意义的损伤。HR是修复在S期出现的单端DSB的主要途径，当复制叉遇到单链断裂或碱基损伤时。在这里，我们讨论了最近的研究结果，即在后期S或G2期由X射线或γ射线直接诱导的两端DSB主要由NHEJ修复，HR仅修复此类DSB的一小部分。该亚级分代表DSB，其定位于异染色质DNA区域，并且在对照细胞中，其在照射后许多小时内以缓慢的动力学修复。所定义的DSB群体由NHEJ或HR修复的观察结果表明，这两个过程中的每一个都分配了特定的任务。此外，重离子诱导的复杂DSB，这是在一般情况下更缓慢地修复比X-或γ-射线诱导的断裂，几乎总是由HR独立的染色质定位修复，这表明修复的速度是一个重要的因素，确定DSB修复途径的使用。最后，在某些条件下，NHEJ和HR也可以相互补偿，使得如果遗传故障需要通路转换，则通常由一种通路修复的DSB可以通过另一种通路进行修复。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。放射治疗与肿瘤学101（2011）7-12
DNA double-strand breaks (DSBs) represent the most biologically significant lesions induced by ionizing radiation (IR). HR is the predominant pathway for repairing one-ended DSBs arising in S-phase when the replication fork encounters single-stranded breaks or base damages. Here, we discuss recent findings that two-ended DSBs directly induced by X- or gamma-rays in late S- or G2-phase are repaired predominantly by NHEJ, with HR only repairing a sub-fraction of such DSBs. This sub-fraction represents DSBs which localize to heterochromatic DNA regions and, which in control cells, are repaired with slow kinetics over many hours post irradiation. The observation that defined DSB populations are repaired by either NHEJ or HR suggests an assignment of specific tasks for each of the two processes. Furthermore, heavy ion induced complex DSBs, which are in general more slowly repaired than X- or gamma-ray induced breaks, are nearly always repaired by HR independent of chromatin localization suggesting that the speed of repair is an important factor determining the DSB repair pathway usage. Finally, NHEJ and HR can, under certain conditions, also compensate for each other such that DSBs normally repaired by one pathway can undergo repair by the other if genetic failures necessitate the pathway switch. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 7-12