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The Deubiquitylating Enzyme USP4 Cooperates with CtIP in DNA Double-Strand Break End Resection

Authors :
Hailong Liu
Haoxing Zhang
Xiaohui Wang
Qingsong Tian
Zhaohua Hu
Changmin Peng
Pei Jiang
TingTing Wang
Wei Guo
Yali Chen
Xinzhi Li
Pumin Zhang
Huadong Pei
Source :
Cell Reports, Vol 13, Iss 1, Pp 93-107 (2015)
Publication Year :
2015
Publisher :
Elsevier, 2015.

Abstract

DNA end resection is a highly regulated and critical step in DNA double-stranded break (DSB) repair. In higher eukaryotes, DSB resection is initiated by the collaborative action of CtIP and the MRE11-RAD50-NBS1 (MRN) complex. Here, we find that the deubiquitylating enzyme USP4 directly participates in DSB resection and homologous recombination (HR). USP4 confers resistance to DNA damage-inducing agents. Mechanistically, USP4 interacts with CtIP and MRN via a specific, conserved region and the catalytic domain of USP4, respectively, and regulates CtIP recruitment to sites of DNA damage. We also find that USP4 autodeubiquitylation is essential for its HR functions. Collectively, our findings identify USP4 as a key regulator of DNA DSB end resection.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
22111247
Volume :
13
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Cell Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.610261e7f9f142a685f7431a04fb0afe
Document Type :
article
Full Text :
https://doi.org/10.1016/j.celrep.2015.08.056