RAD18 activates the G2/M checkpoint through DNA damage signaling to maintain genome integrity after ionizing radiation exposure.
RAD18 activates the G2/M checkpoint through DNA damage signaling to maintain genome integrity after ionizing radiation exposure.
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DOI：
10.1371/journal.pone.0117845
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kamiya K
中科院分区：
文献类型：
--
作者：
Sasatani M;Xu Y;Kawai H;Cao L;Tateishi S;Shimura T;Li J;Iizuka D;Noda A;Hamasaki K;Kusunoki Y;Kamiya K
泛素连接酶RAD 18通过其向停滞的复制叉的募集以及其在增殖细胞核抗原（PCNA）的泛素化中的作用而参与复制后修复途径。最近，有报道称，RAD 18也被募集到DNA双链断裂（DSB）位点，在电离辐射（IR）诱导的DNA损伤反应中发挥新的功能。这种新的作用是独立的PCNA泛素化，但很少有人知道如何RAD 18功能后，IR曝光。在这里，我们描述了一个作用，RAD 18在IR诱导的DNA损伤信号通路在细胞周期的G2/M期。RAD 18耗竭细胞减少了DNA损伤信号因子ATM、γ H2 AX和53 BP 1在IR暴露后G2/M期细胞中的聚集，并减弱了G2/M检查点的激活。此外，在体外和体内，RAD 18的耗竭增加了IR暴露后的微核形成和细胞死亡。我们的数据表明，RAD 18可以作为DNA损伤反应信号的介导者，激活G2/M检查点，以维持基因组的完整性和细胞存活后，IR暴露。
The ubiquitin ligase RAD18 is involved in post replication repair pathways via its recruitment to stalled replication forks, and its role in the ubiquitylation of proliferating cell nuclear antigen (PCNA). Recently, it has been reported that RAD18 is also recruited to DNA double strand break (DSB) sites, where it plays novel functions in the DNA damage response induced by ionizing radiation (IR). This new role is independent of PCNA ubiquitylation, but little is known about how RAD18 functions after IR exposure. Here, we describe a role for RAD18 in the IR-induced DNA damage signaling pathway at G2/M phase in the cell cycle. Depleting cells of RAD18 reduced the recruitment of the DNA damage signaling factors ATM, γH2AX, and 53BP1 to foci in cells at the G2/M phase after IR exposure, and attenuated activation of the G2/M checkpoint. Furthermore, depletion of RAD18 increased micronuclei formation and cell death following IR exposure, both in vitro and in vivo. Our data suggest that RAD18 can function as a mediator for DNA damage response signals to activate the G2/M checkpoint in order to maintain genome integrity and cell survival after IR exposure.
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影响因子：
14.9
作者：
Masuda Y;Suzuki M;Kawai H;Suzuki F;Kamiya K
通讯作者：
Kamiya K
影响因子：
64.8
作者：
Stewart, GS;Wang, B;Elledge, SJ
通讯作者：
Elledge, SJ
RAD18 传递 DNA 损伤信号以引发同源重组修复。
影响因子：
21.3
作者：
Huang, Jun;Huen, Michael S. Y.;Kim, Hongtae;Leung, Charles Chung Yun;Glover, J. N. Mark;Yu, Xiaochun;Chen, Junjie
通讯作者：
Chen, Junjie
影响因子：
3.7
作者：
Inagaki A;Sleddens-Linkels E;van Cappellen WA;Hibbert RG;Sixma TK;Hoeijmakers JH;Grootegoed JA;Baarends WM
通讯作者：
Baarends WM
影响因子：
64.8
作者：
Lou, ZK;Minter-Dykhouse, K;Chen, JJ
通讯作者：
Chen, JJ