A Process of Resection-Dependent Nonhomologous End Joining Involving the Goddess Artemis.
A Process of Resection-Dependent Nonhomologous End Joining Involving the Goddess Artemis.
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DOI：
10.1016/j.tibs.2017.06.011
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发表时间：
2017-09
影响因子：
13.8
通讯作者：
Jeggo P
中科院分区：
文献类型：
--
作者：
Löbrich M;Jeggo P
DNA双链断裂(DSB)是一种危险的损伤形式，可能导致细胞死亡或基因组重排。在哺乳动物的G1期和G2期细胞中，双链断裂是以双组分动力学方式修复的。在这两个阶段，一个快速的过程使用规范的非同源末端连接(c-NHEJ)来修复大多数DSB。在G2中，通过同源重组进行缓慢修复。G1中缓慢的修复过程也涉及c-NHEJ蛋白，但另外需要核酸酶Artemis和DNA末端切除。在这里，我们考虑了G1中DSB缓慢修复的性质，并评估了决定DSB修复速度是快还是慢的因素。我们考虑了我们目前知识的局限性，并为Artemis依赖的c-NHEJ及其使用环境提供了一个推测模型。已经定义了一条c-NHEJ途径，包括在G1期结扎之前切除DSB末端。因此，在G1期人类细胞中修复DSB的两条主要途径是切除非依赖的和切除依赖的c-NHEJ。G1中的切除过程使用了许多与G2中同源重组时用于切除的相同因素，但以适合c-NHEJ过程的方式协调它们。由于Artemis是切除过程中唯一被识别的因素，其丢失导致未修复的DSB，我们将这一过程称为Artemis和切除依赖的c-NHEJ。其他切除因素的丧失阻止了切除的开始，但允许不依赖于切除的c-NHEJ。依赖Artemis和切除的c-NHEJ对易位的形成做出了重要贡献，并可能导致先前描述的微同源介导的末端连接。
DNA double-strand breaks (DSBs) are a hazardous form of damage that can potentially cause cell death or genomic rearrangements. In mammalian G1- and G2-phase cells, DSBs are repaired with two-component kinetics. In both phases, a fast process uses canonical nonhomologous end joining (c-NHEJ) to repair the majority of DSBs. In G2, slow repair occurs by homologous recombination. The slow repair process in G1 also involves c-NHEJ proteins but additionally requires the nuclease Artemis and DNA end resection. Here, we consider the nature of slow DSB repair in G1 and evaluate factors determining whether DSBs are repaired with fast or slow kinetics. We consider limitations in our current knowledge and present a speculative model for Artemis-dependent c-NHEJ and the environment underlying its usage. A c-NHEJ pathway has been defined involving resection of DSB ends prior to their ligation in G1. Thus, the two main pathways for repairing DSBs in G1 human cells are resection-independent and resection-dependent c-NHEJ. The resection process in G1 uses many of the same factors used for resection during homologous recombination in G2 but orchestrates them in a manner suited to a c-NHEJ process. Since Artemis is the only identified factor involved in the resection process whose loss leads to unrepaired DSBs, we refer to this process as Artemis- and resection-dependent c-NHEJ. Loss of other resection factors prevents the initiation of resection but allows resection-independent c-NHEJ. Artemis- and resection-dependent c-NHEJ makes a major contribution to translocation formation and can lead to previously described microhomology-mediated end joining.
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DOI：
10.1083/jcb.201401146
发表时间：
2014-09-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Barton O;Naumann SC;Diemer-Biehs R;Künzel J;Steinlage M;Conrad S;Makharashvili N;Wang J;Feng L;Lopez BS;Paull TT;Chen J;Jeggo PA;Löbrich M
通讯作者：
Löbrich M
DOI：
10.1073/pnas.1016045108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Asaithamby, Aroumougame;Hu, Burong;Chen, David J.
通讯作者：
Chen, David J.
由 53BP1-RIF1 和 BRCA1-CtIP 组成的细胞周期依赖性调节回路控制 DNA 修复途径的选择。
影响因子：
16
作者：
Escribano-Diaz, Cristina;Orthwein, Alexandre;Durocher, Daniel
通讯作者：
Durocher, Daniel
影响因子：
14.9
作者：
Chang HH;Lieber MR
通讯作者：
Lieber MR
影响因子：
16.6
作者：
Chakraborty, Anirban;Tapryal, Nisha;Venkova, Tatiana;Horikoshi, Nobuo;Pandita, Raj K.;Sarker, Altaf H.;Sarkar, Partha S.;Pandita, Tej K.;Hazra, Tapas K.
通讯作者：
Hazra, Tapas K.