RNF126 Quenches RNF168 Function in the DNA Damage Response.
10.1016/j.gpb.2018.07.004
- Author:
Lianzhong ZHANG
1
,
2
;
Zhenzhen WANG
3
;
Ruifeng SHI
1
,
4
;
Xuefei ZHU
5
;
Jiahui ZHOU
3
;
Bin PENG
5
;
Xingzhi XU
1
,
6
Author Information
1. College of Life Sciences, Capital Normal University, Beijing 100048, China
2. Faculty of Life Sciences, Tangshan Normal College, Tangshan 063000, China.
3. College of Life Sciences, Capital Normal University, Beijing 100048, China.
4. Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen 518060, China.
5. Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen 518060, China.
6. Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University Health Science Center, Shenzhen 518060, China. Electronic address: Xingzhi.Xu@szu.edu.cn.
- Publication Type:Journal Article
- Keywords:
DNA damage response;
DNA repair;
RNF126;
RNF168;
RNF8;
Ubiquitination
- MeSH:
Carrier Proteins;
metabolism;
Cell Line, Tumor;
DNA Breaks, Double-Stranded;
DNA Repair;
genetics;
DNA-Binding Proteins;
metabolism;
Genomic Instability;
HeLa Cells;
Histones;
metabolism;
Humans;
Nuclear Proteins;
metabolism;
RNA Interference;
RNA, Small Interfering;
genetics;
Signal Transduction;
Tumor Suppressor p53-Binding Protein 1;
metabolism;
Ubiquitin;
Ubiquitin-Protein Ligases;
genetics;
metabolism;
Ubiquitination
- From:
Genomics, Proteomics & Bioinformatics
2018;16(6):428-438
- CountryChina
- Language:English
-
Abstract:
DNA damage response (DDR) is essential for maintaining genome stability and protecting cells from tumorigenesis. Ubiquitin and ubiquitin-like modifications play an important role in DDR, from signaling DNA damage to mediating DNA repair. In this report, we found that the E3 ligase ring finger protein 126 (RNF126) was recruited to UV laser micro-irradiation-induced stripes in a RNF8-dependent manner. RNF126 directly interacted with and ubiquitinated another E3 ligase, RNF168. Overexpression of wild type RNF126, but not catalytically-inactive mutant RNF126 (CC229/232AA), diminished ubiquitination of H2A histone family member X (H2AX), and subsequent bleomycin-induced focus formation of total ubiquitin FK2, TP53-binding protein 1 (53BP1), and receptor-associated protein 80 (RAP80). Interestingly, both RNF126 overexpression and RNF126 downregulation compromised homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs). Taken together, our findings demonstrate that RNF126 negatively regulates RNF168 function in DDR and its appropriate cellular expression levels are essential for HR-mediated DSB repair.
