USP11 acts as a histone deubiquitinase functioning in chromatin reorganization during DNA repair

被引：56

作者：

Ting, Xia ^{[1
]}

Xia, Lu ^{[1
]}

Yang, Jianguo ^{[1
,2
]}

He, Lin ^{[1
,3
]}

Si, Wenzhe ^{[4
]}

Shang, Yongfeng ^{[1
,3
]}

Sun, Luyang ^{[1
,2
,5
]}

机构：

[1] Peking Univ, Key Lab Carcinogenesis & Translat Res, Minist Educ, Dept Biochem & Mol Biol,Hlth Sci Ctr,Sch Basic Me, Beijing 100191, Peoples R China

[2] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Integrat Chinese & Western Med, Beijing 100191, Peoples R China

[3] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China

[4] Peking Univ, Hosp 3, Dept Lab Med, Beijing 100191, Peoples R China

[5] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China

来源：

NUCLEIC ACIDS RESEARCH | 2019年 / 47卷 / 18期

基金：

中国国家自然科学基金;

关键词：

DOUBLE-STRAND BREAKS; DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; DEPHOSPHORYLATES GAMMA-H2AX; UBIQUITIN; H2B; COMPLEX; UBIQUITYLATION; ACETYLATION; COUNTERACTS;

D O I：

10.1093/nar/gkz726

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：

How chromatin dynamics is regulated to ensure efficient DNA repair remains to be understood. Here, we report that the ubiquitin-specific protease USP11 acts as a histone deubiquitinase to catalyze H2AK119 and H2BK120 deubiquitination. We showed that USP11 is physically associated with the chromatin remodeling NuRD complex and functionally involved in DNA repair process. We demonstrated that USP11-mediated histone deubiquitination and NuRD-associated histone deacetylation coordinate to allow timely termination of DNA repair and reorganization of the chromatin structure. As such, USP11 is involved in chromatin condensation, genomic stability, and cell survival. Together, these observations indicate that USP11 is a chromatin modifier critically involved in DNA damage response and the maintenance of genomic stability.

引用

页码：9721 / 9740

页数：20

共 102 条

[1] Hypersensitivity of nonhomologous DNA end-joining mutants to VP-16 and ICRF-193 - Implications for the repair of topoisomerase II-mediated DNA damage [J].