PCNA Confers the Conversion of Hepatitis B Virus Relaxed Circular DNA to Covalently Closed Circular DNA by Its DNA Binding Domain
10.13865/j.cnki.cjbmb.2021.05.1122
- Author:
Ying YUAN
1
;
Jin-Yan FENG
1
;
Li-Na ZHAO
1
;
Guang YANG
1
;
Man ZHAO
1
;
Hong-Feng YUAN
1
;
Hao-Lin YUN
1
;
Zi-Xian LIU
1
;
Xiao-Dong ZHANG
1
;
Yue-Guo LI
2
Author Information
1. Department of Cancer Research, College of Life Sciences, Nankai University
2. Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National ClinicalResearch Cancer for Cancer
- Publication Type:Journal Article
- Keywords:
covalently closed circular DNA (cccDNA);
DNA binding domain;
hepatitis B virus (HBV);
proliferating cell nuclear antigen (PCNA);
relaxed circular DNA (rcDNA)
- From:
Chinese Journal of Biochemistry and Molecular Biology
2021;37(9):1197-1204
- CountryChina
- Language:Chinese
-
Abstract:
Chronic hepatitis B virus (HBV) infection is a primary cause for liver cancer. And the main challenge of curing hepatitis B is the elimination of the stable covalently closed circular DNA (cccDNA) of the viral genome. The formation of HBV cccDNA requires the filling of single-stranded region and the ligation of nicks in relaxed circular DNA (rcDNA) strands. Previously, our group reported that proliferating cell nuclear antigen (PCNA) was involved in the formation of HBV cccDNA. However, the underlying mechanism of the conversion of HBV rcDNA to cccDNA is poorly understood. In the present study, we aim to explore the mechanism by which PCNA contributes to the conversion of HBV rcDNA to cccDNA. Our data showed that PCNA was involved in the process of HBV rcDNA repair. The knockout of PCNA by the CRISPR/Cas9 system remarkably blocked the conversion of HBV rcDNA to cccDNA, while the ectopic expression of PCNA could effectively rescue the event (P<0. 001). Knockout of PCNA significantly slowed down the conversion kinetics of HBV rcDNA to cccDNA (P<0. 01). Mechanically, the DNA binding domain of PCNA was required for the process of HBV rcDNA repair to cccDNA (P<0. 01). Thus, we conclude that PCNA confers the conversion of HBV rcDNA to cccDNA by its DNA binding domain. Clinically, PCNA might serve as a novel target for antiviral therapy.
