Autophagy substrate SQSTM1/p62 regulates chromatin ubiquitination during the DNA damage response

被引：44

作者：

Wang, Yanan ^{[1
]}

Zhu, Wei-Guo ^{[1
,2
,3
]}

Zhao, Ying ^{[1
]}

机构：

[1] Peking Univ, Beijing Key Lab Prot Posttranslat Modificat & Cel, Key Lab Carcinogenesis & Translat Res,Hlth Sci Ct, Minist Educ,Dept Biochem & Mol Biol,Sch Basic Med, Beijing 100191, Peoples R China

[2] Peking Tsinghua Univ, Ctr Life Sci, Beijing, Peoples R China

[3] Shenzhen Univ, Sch Med, Shenzhen, Peoples R China

来源：

AUTOPHAGY | 2017年 / 13卷 / 01期

关键词：

autophagy; DNA damage; histone ubiquitination; p62; RNF168;

D O I：

10.1080/15548627.2016.1245262

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The importance of autophagy in the DNA damage repair process is clear; however, the detailed molecular mechanism is still largely unknown. Here we found that DNA damage-induced histone H2A ubiquitination is suppressed in autophagy-deficient cells in a SQSTM1/p62 dependent manner. SQSTM1 binds and inhibits E3 ligase RNF168s activity, which is essential for H2A ubiquitination. As a result, several important factors for DNA repair cannot be recruited to the sites of DNA double-strand breaks (DSBs) in autophagy-deficient cells, leading to diminished DNA repair and increased sensitivity of cells to radiation.

引用

页码：212 / 213

页数：2