期刊
ONCOTARGET
卷 8, 期 2, 页码 2197-2208出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11116
关键词
USP19; HDAC1/2; DNA repair; genome stability
资金
- Collaborative Innovation Center for Biotherapy
- National Basic Research Program of China [2013CB910302, 2014CB910603, 2012CB910701]
- China National High Technology Research and Development Program [2014AA020612, 2014AA020604]
- International Science and Technology Cooperation Program of China [2015DFA31610]
- National Natural Science Foundation of China [81325014, 81221004, 31271447, 81130037, 81402314, 31370761, 31370915]
- Bejing municipal science and technology commission [2016108]
Excessive accumulation of DNA damage will generate chromosome stress, leading to various chromosome abnormalities such as chromatin bridge and result in genomic instability. Orchestra procession and regulation of DNA damage repair are vital for keeping genome stability. Despite of the key role of HDAC1/2 in double strand break (DSB) repair, the regulation for their mode of action is less well understood. In this study, we found that deubiquitination enzymes USP19 physically interacts with HDAC1/2 and specifically regulate their K63-linked ubiquitination, which might be crucial for regulation of HDAC1/2 activity in DNA damage repair. Notably, we found that USP19 trans-locate into nucleus upon IR irradiation and is indispensable for normally DNA damage response. In addition, we showed that USP19 play critical role in preventing anaphase bridge formation through regulating DNA damage repair process. Furthermore, the expression level of USP19 is commonly lower or deleted in several types of tumor. These results indicated that USP19 is a key factor in modulating DNA damage repair by targeting HDAC1/2 K63-linked ubiquitination, cells with deletion or decreased expression of USP19 might cause genome instability and even contribute to tumorigenesis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据