Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs

doi:10.1016/j.cellsig.2017.04.023

	Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs
	You, Xue1,2 ; Guo, Weiwei 1; Wang, Lin 1; Hou, Yongfan 1; Zhang, Huanhuan1,2 ; Pan, Yi 1; Han, Ruomei1,2 ; Huang, Meiqin 1; Liao, Lujian 3; Chen, Yan1,2
	2017-08
发表期刊	CELLULAR SIGNALLING (IF:4.4[JCR-2023],4.4[5-Year])
ISSN	0898-6568
卷号	36 页码:108-116
发表状态	已发表
DOI	10.1016/j.cellsig.2017.04.023
摘要	The RAD23B-XPC complex in the nucleus plays a key role in the initial damage recognition during global genome nucleotide excision repair (NER). Within the complex, XPC, a product of Xeroderma pigmentosum C, recognizes and interacts with the unpaired bases in the undamaged DNA strand, while RAD23B stabilizes XPC. However, how RAD23B is regulated by other factors is not well known. We report here a mode of spatial regulation of RAD23B that controls XPC stability and DNA damage repair. We first identified that RAD23B was able to directly associate with PAQR3, a newly-discovered tumor suppressor implicated in many types of human cancers. PAQR3 reduced the protein level of XPC, together with accelerated degradation and enhanced polyubiquitination of XPC. Mechanistically, PAQR3 reduces nucleic distribution of RAD23B by tethering it to the Golgi apparatus, thus diminishing the amount of RAD23B proteins available to interact with XPC in the nucleus. The viability of gastric cancer cells upon treatment with chemotherapy drugs including etoposide, cisplatin and doxorubicin was reduced by PAQR3 overexpression, but enhanced by PAQR3 knockdown. The degree of DNA damage induced by these drugs, as measured by immunoblotting with gamma-H2AX, was elevated by PAQR3 overexpression and lessened by PAQR3 knockdown. Furthermore, a synthetic peptide comprising the N-terminus of PAQR3 was able to recapitulate the activity of PAQR3 in reducing XPC stability and enhancing chemotherapy drug-induced DNA damage. In conclusion, our study reveals that RAD23B is controlled by subcellular compartmentation, thus affecting XPC-mediated DNA damage repair in cancer cells.
关键词	DNA damage repair RAD23B XPC Ubiquitination Compartmentation
收录类别	SCI
语种	英语
资助项目	Chinese Academy of Sciences[XDA12010102] ; Chinese Academy of Sciences[QYZDJ-SSW-SMC008] ; Chinese Academy of Sciences[ZDRW-ZS-2016-8]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000405044000011
出版者	ELSEVIER SCIENCE INC
WOS关键词	NUCLEOTIDE EXCISION-REPAIR ; GROUP-C PROTEIN ; PAQR3 ; COMPLEX ; CANCERS ; IDENTIFICATION ; RECOGNITION ; METASTASIS ; EXPRESSION ; RECEPTORS
原始文献类型	Article
通讯作者	Chen, Yan
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2879
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_陈雁组生命科学与技术学院_硕士生生命科学与技术学院_博士生
通讯作者	Chen, Yan
作者单位	1.Chinese Acad Sci, CAS Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Univ Chinese Acad Sci, Shanghai 200031, Peoples R China 2.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 3.East China Normal Univ, Sch Life Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	You, Xue,Guo, Weiwei,Wang, Lin,et al. Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs[J]. CELLULAR SIGNALLING,2017,36:108-116.
APA	You, Xue.,Guo, Weiwei.,Wang, Lin.,Hou, Yongfan.,Zhang, Huanhuan.,...&Chen, Yan.(2017).Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs.CELLULAR SIGNALLING,36,108-116.
MLA	You, Xue,et al."Subcellular distribution of RAD23B controls XPC degradation and DNA damage repair in response to chemotherapy drugs".CELLULAR SIGNALLING 36(2017):108-116.