The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair   in host cells via deubiquitination of proliferating cell nuclear antigen

doi:10.1074/jbc.M117.778076

CORC > 北京大学 > 生命科学学院

	The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen
	Dong, Xiaodong ; Guan, Junhong ; Zheng, Chunfu ; Zheng, Xiaofeng
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2017
关键词	LARGE TEGUMENT PROTEIN POLYMERASE-ETA MONOUBIQUITINATED PCNA DAMAGE REPLICATION PATHWAY TYPE-1 DOMAIN VP1/2 UBIQUITINATION
DOI	10.1074/jbc.M117.778076
英文摘要	Herpes simplex virus 1 (HSV-1) infection manipulates distinct host DNA-damage responses to facilitate virus proliferation, but the molecular mechanisms remain to be elucidated. One possible HSV-1 target might be DNA damage-tolerance mechanisms, such as the translesion synthesis (TLS) pathway. In TLS, proliferating cell nuclear antigen (PCNA) is monoubiquitinated in response to DNA damage-caused replication fork stalling. Ubiquitinated PCNA then facilitates the error-prone DNA polymerase eta (pol eta)-mediated TLS, allowing the fork to bypass damaged sites. Because of the involvement of PCNA ubiquitination in DNA-damage repair, we hypothesized that the function of PCNA might be altered by HSV-1. Here we show that PCNA is a substrate of the HSV-1 deubiquitinase UL36USP, which has previously been shown to be involved mainly in virus uptake and maturation. In HSV-1-infected cells, viral infection-associated UL36USP consistently reduced PCNA ubiquitination. The deubiquitination of PCNA inhibited the formation of pol eta foci and also increased cell sensitivity to DNA-damage agents. Moreover, the catalytically inactive mutant UL36C40A failed to deubiquitinate PCNA. Of note, the levels of virus marker genes increased strikingly in cells infected with wild-type HSV-1, but only moderately in UL36C40A mutant virus-infected cells, indicating that the UL36USP deubiquitinating activity supports HSV-1 virus replication during infection. These findings suggest a role of UL36USP in the DNA damage-response pathway.; National Science Foundation of China [31470754, 31670786]; National Key Research and Development Program of China [2016YFC1302401]; Doctoral Fund of Ministry of Education of China [20130001130003]; SCI(E); ARTICLE; 20; 8472-8483; 292
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/473351]
专题	生命科学学院
推荐引用方式 GB/T 7714	Dong, Xiaodong,Guan, Junhong,Zheng, Chunfu,et al. The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017.
APA	Dong, Xiaodong,Guan, Junhong,Zheng, Chunfu,&Zheng, Xiaofeng.(2017).The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen.JOURNAL OF BIOLOGICAL CHEMISTRY.
MLA	Dong, Xiaodong,et al."The herpes simplex virus 1 UL36USP deubiquitinase suppresses DNA repair in host cells via deubiquitination of proliferating cell nuclear antigen".JOURNAL OF BIOLOGICAL CHEMISTRY (2017).