A miR-590/Acvr2a/Rad51b axis regulates DNA damage repair during mESC proliferation.
A miR-590/Acvr2a/Rad51b axis regulates DNA damage repair during mESC proliferation.
复制标题
miR-590/acvr2a/rad51b轴调节MESC增殖期间的DNA损伤修复。
DOI：
10.1016/j.stemcr.2014.10.006
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发表时间：
2014-12-09
影响因子：
5.9
通讯作者：
Kang, Jiuhong
中科院分区：
文献类型：
--
作者：
Liu, Qidong;Wang, Guiying;Chen, Yafang;Li, Guoping;Yang, Dandan;Kang, Jiuhong
胚胎干细胞（ESC）能够快速增殖，这也会导致DNA损伤。为了在快速增殖过程中保持基因组的稳定，ESCs必须具有有效的抑制遗传毒性应激的系统。在这里，我们表明，白血病抑制因子（LIF），保持小鼠胚胎干细胞（mESCs）的自我更新能力的撤回，显着抑制细胞增殖和DNA损伤的mESCs和上调miR-590的表达。miR-590促进单链断裂（SSB）和双链断裂（DSB）损伤修复，从而减缓mESC的增殖而不影响干性。miR-590直接靶向激活素受体2a（Acvr 2a）以介导激活素信号传导。我们鉴定了同源重组介导的修复（HRR）基因Rad 51 b，作为调节SSB和DSB损伤修复和细胞周期的miR-590/Acvr 2a通路的下游分子。我们的研究表明，miR-590/Acvr 2a/Rad 51 b信号轴通过平衡DNA损伤修复和自我更新期间的快速增殖来确保mESCs的稳定。miR-590/Acvr 2a/Rad 51 b轴平衡mESC中的SSB和DSB损伤修复在这篇文章中，Kang和同事们表明，miR-590促进DNA单链断裂和双链断裂损伤修复，通过直接靶向Acvr 2a减缓mESC的增殖。他们进一步确定Rad 51 b受miR-590/Acvr 2a通路的调节，并参与miR-590/Acvr 2a/Rad 51 b信号轴的形成，以平衡mESC自我更新过程中的DNA损伤修复和快速增殖。
Embryonic stem cells (ESCs) enable rapid proliferation that also causes DNA damage. To maintain genomic stabilization during rapid proliferation, ESCs must have an efficient system to repress genotoxic stress. Here, we show that withdrawal of leukemia inhibitory factor (LIF), which maintains the self-renewal capability of mouse ESCs (mESCs), significantly inhibits the cell proliferation and DNA damage of mESCs and upregulates the expression of miR-590. miR-590 promotes single-strand break (SSB) and double-strand break (DSB) damage repair, thus slowing proliferation of mESCs without influencing stemness. miR-590 directly targets Activin receptor type 2a (Acvr2a) to mediate Activin signaling. We identified the homologous recombination-mediated repair (HRR) gene, Rad51b, as a downstream molecule of the miR-590/Acvr2a pathway regulating the SSB and DSB damage repair and cell cycle. Our study shows that a miR-590/Acvr2a/Rad51b signaling axis ensures the stabilization of mESCs by balancing DNA damage repair and rapid proliferation during self-renewal. miR-590 promotes DNA damage repair and slows proliferation by targeting Acvr2a miR-590/Acvr2a/Rad51b axis balances SSB and DSB damage repair in mESCs In this article, Kang and colleagues show that miR-590 promotes DNA single-strand break and double-strand break damage repair, slowing proliferation of mESCs by directly targeting Acvr2a. They further identified that Rad51b was regulated by miR-590/Acvr2a pathway and involved in the formation of the miR-590/Acvr2a/Rad51b signaling axis to balance the DNA damage repair and rapid proliferation during mESC self-renewal.
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DOI：
10.1186/bcr3368
发表时间：
2012-12-07
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Fordyce CA;Patten KT;Fessenden TB;DeFilippis R;Hwang ES;Zhao J;Tlsty TD
通讯作者：
Tlsty TD
影响因子：
3.8
作者：
Jensen, Ryan B.;Ozes, Ali;Kim, Taeho;Estep, Allison;Kowalczykowski, Stephen C.
通讯作者：
Kowalczykowski, Stephen C.
影响因子：
5.3
作者：
Donoho, G;Jasin, M;Berg, P
通讯作者：
Berg, P
影响因子：
3.1
作者：
Ishikawa, Kazuhiro;Ishii, Hideshi;Saito, Toshiyuki
通讯作者：
Saito, Toshiyuki
影响因子：
4.3
作者：
Chuykin, Ilya A.;Lianguzova, Maria S.;Pospelov, Valery A.
通讯作者：
Pospelov, Valery A.