RMI1 contributes to DNA repair and to the tolerance to camptothecin

被引：9

作者：

Fang, Lianying ^{[1
,2
,3
]}

Sun, Xiaohui ^{[1
,2
]}

Wang, Yan ^{[1
,2
]}

Du, Liqing ^{[1
,2
]}

Ji, Kaihua ^{[1
,2
]}

Wang, Jinhan ^{[1
,2
]}

He, Ningning ^{[1
,2
]}

Liu, Yang ^{[1
,2
]}

Wang, Qin ^{[1
,2
]}

Zhai, Hezheng ^{[1
,2
]}

Hao, Jianxiu ^{[1
,2
]}

Xu, Chang ^{[1
,2
,4
]}

Liu, Qiang ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, Inst Radiat Med, Tianjin Key Lab Radiat Med & Mol Nucl Med, 238 Baidi Rd, Tianjin, Peoples R China

[2] Peking Union Med Coll, 238 Baidi Rd, Tianjin, Peoples R China

[3] Shandong Acad Med Sci, Radiat Med Inst, Jinan, Peoples R China

[4] Nankai Univ, State Key Lab Med Chem Biol, Tianjin, Peoples R China

来源：

FASEB JOURNAL | 2019年 / 33卷 / 04期

基金：

中国国家自然科学基金;

关键词：

double-strand breaks; RAD51; genome instability; HUMAN RECQ HELICASES; REPLICATION STRESS; MRN COMPLEX; DAMAGE RESPONSE; ACTIVATION; DISTINCT;

D O I：

10.1096/fj.201802014R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Maintenance of genome integrity is critical for faithful propagation of genetic information and the prevention of the mutagenesis induced by various DNA damage events. RecQ-mediated genome instability protein 1 (RMI1), together with Bloom syndrome protein and topoisomerase III alpha, form an evolutionarily conserved complex that is critical for the maintenance of genomic stability. Herein, we report that RMI1 depletion increases cell sensitivity to camptothecin treatment, as shown by an elevation of genotoxic stress-induced DNA double-strand breaks, a stronger activation of the DNA damage response, and a greater G2/M cell cycle delay. Our findings support that, upon DNA damage, RMI1 forms nuclear foci at the damaged regions, interacts with RAD51, and facilitates the recruitment of RAD51 to initiate homologous recombination. Our data reveal the importance of RMI1 in response to DNA double-strand breaks and shed light on the molecular mechanisms by which RMI1 contributes to maintain genome stability.

引用

页码：5561 / 5570

页数：10