例如:"lncRNA", "apoptosis", "WRKY"

Cadmium disrupts the DNA damage response by destabilizing RNF168.

Food Chem. Toxicol.2019 Nov;133:110745. Epub 2019 Jul 31
Shuyuan Zhang 1 , Shuailin Hao 1 , Zhiyu Qiu 1 , Ya Wang 1 , Yuqin Zhao 1 , Youhang Li 1 , Wen Gao 1 , Yan Wu 1 , Chang Liu 1 , Xingzhi Xu 2 , Hailong Wang 3
Shuyuan Zhang 1 , Shuailin Hao 1 , Zhiyu Qiu 1 , Ya Wang 1 , Yuqin Zhao 1 , Youhang Li 1 , Wen Gao 1 , Yan Wu 1 , Chang Liu 1 , Xingzhi Xu 2 , Hailong Wang 3
+ et al

[No authors listed]

Author information
  • 1 Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing, 100048, China.
  • 2 Guangdong Key Laboratory for Genome Stability & Disease Prevention, Shenzhen University School of Medicine, Shenzhen, Guangdong, 518060, China.
  • 3 Beijing Key Laboratory of DNA Damage Response and College of Life Sciences, Capital Normal University, Beijing, 100048, China. Electronic address: Hailwang@cnu.edu.cn.

摘要


Cadmium (Cd) is a dispensable element for the human body and is usually considered a carcinogen. Occupational and environmental Cd exposure leads to sustained cellular proliferation in some tissues and tumorigenesis via an unclear mechanism. Here, we evaluated the role of Cd in the DNA damage response (DDR). We found that Cd exposure causes extensive DNA double-strand breaks (DSBs) and prevents accumulation of ubiquitination signals at these sites of DNA damage. Cd treatment compromises 53BP1 and BRCA1 recruitment to DSBs induced by itself or DNA damaging agents and partially inactivates the G2/M checkpoint. Mechanistically, Cd directly binds to the E3 ubiquitin ligase RNF168, induces the ubiquitin-proteasome pathway that mediates RNF168 degradation and suppresses RNF168 ubiquitin-ligase activity in vitro. Our study raises the possibility that Cd may target RNF168 to disrupt proper DSB signaling in cultured cells. This pathway may represent a novel mechanism for carcinogenesis induced by Cd.

KEYWORDS: Cadmium, DNA damage response, Double-stranded break, RNF168, Ubiquitination