DNA polymerase η promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1.
DNA polymerase η promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1.
复制标题
DNA聚合酶η可促进非同源末端连接，依托泊苷暴露取决于脚手架蛋白KAP1。
DOI：
10.1016/j.jbc.2022.101861
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发表时间：
2022-05
影响因子：
4.8
通讯作者：
Guo, Caixia
中科院分区：
文献类型：
--
作者：
Ma, Xiaolu;Wang, Chen;Zhou, Bo;Cheng, Zina;Mao, Zhiyong;Tang, Tie-Shan;Guo, Caixia
DNA polymerase eta (Pol η) is a eukaryotic member of the Y-family of DNA polymerase involved in translesion DNA synthesis and genome mutagenesis. Recently, several translesion DNA synthesis polymerases have been found to function in repair of DNA double-strand breaks (DSBs). However, the role of Pol η in promoting DSB repair remains to be well defined. Here, we demonstrated that Pol η could be targeted to etoposide (ETO)-induced DSBs and that depletion of Pol η in cells causes increased sensitivity to ETO. Intriguingly, depletion of Pol η also led to a nonhomologous end joining repair defect in a catalytic activity–independent manner. We further identified the scaffold protein Kap1 as a novel interacting partner of Pol η, the depletion of which resulted in impaired formation of Pol η and Rad18 foci after ETO treatment. Additionally, overexpression of Kap1 failed to restore Pol η focus formation in Rad18-deficient cells after ETO treatment. Interestingly, we also found that Kap1 bound to Rad18 in a Pol η-dependent manner, and moreover, depletion of Kap1 led to a significant reduction in Rad18–Pol η association, indicating that Kap1 forms a ternary complex with Rad18 and Pol η to stabilize Rad18–Pol η association. Our findings demonstrate that Kap1 could regulate the role of Pol η in ETO-induced DSB repair via facilitating Rad18 recruitment and stabilizing Rad18–Pol η association.
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DOI：
10.1038/nrc2607
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
DOI：
10.4161/cc.7.18.6679
发表时间：
2008-09-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Mao Z;Bozzella M;Seluanov A;Gorbunova V
通讯作者：
Gorbunova V
影响因子：
4.5
作者：
Hendel A;Krijger PH;Diamant N;Goren Z;Langerak P;Kim J;Reissner T;Lee KY;Geacintov NE;Carell T;Myung K;Tateishi S;D'Andrea A;Jacobs H;Livneh Z
通讯作者：
Livneh Z
影响因子：
12.4
作者：
Hedglin M;Benkovic SJ
通讯作者：
Benkovic SJ
影响因子：
5.6
作者：
Chen CY;Kawasumi M;Lan TY;Poon CL;Lin YS;Wu PJ;Chen YC;Chen BH;Wu CH;Lo JF;Weng RR;Sun YC;Hung KF
通讯作者：
Hung KF