Hepatitis C Virus NS3 Protein Plays a Dual Role in WRN-Mediated Repair of Nonhomologous End Joining
Journal
Journal of virology
Journal Volume
93
Journal Issue
22
Pages
-
Date Issued
2019
Author(s)
Abstract
HCV infection is a worldwide problem of public health and a major contributor to hepatocellular carcinoma. The single-stranded RNA virus with RNA-dependent RNA polymerase experiences a high error rate and develops strategies to escape the immune system and hepatocarcinogenesis. Studies have revealed the involvement of HCV proteins in the impairment of DNA repair. The present study aimed to further elucidate mechanisms by which the viral NS3 protein impairs the repair of DNA damage. Our results clearly indicate that HCV NS3/4A protease targets WRN for degradation, and, at the same time, diminishes the repair efficiency of nonhomologous end joining by interfering with the recruitment of Ku protein to the DNA double-strand break sites. The study describes a novel mechanism by which the NS3 protein influences DNA repair and provides new insight into the molecular mechanism of HCV pathogenesis.
SDGs
Other Subjects
DNA; double stranded DNA; Ku antigen; nonstructural protein 3; nonstructural protein 4; proteasome; Werner syndrome ATP dependent helicase; DNA; DNA binding protein; exodeoxyribonuclease; Ku antigen; NS3 protein, hepatitis C virus; RNA directed RNA polymerase; viral protein; Werner syndrome ATP dependent helicase; WRN protein, human; Article; carcinogenesis; cell nucleus; controlled study; DNA end joining repair; DNA repair; DNA strand breakage; enzyme activity; enzyme substrate; gene mutation; genomic instability; Hepatitis C virus; Huh-7 cell line; human; human cell; nonhuman; priority journal; protein degradation; protein expression; protein function; protein interaction; protein localization; protein transport; virus replication; cell line; chronic hepatitis C; DNA damage; double stranded DNA break; genetics; HEK293 cell line; Hepacivirus; metabolism; physiology; Cell Line; DNA; DNA Breaks, Double-Stranded; DNA Damage; DNA End-Joining Repair; DNA Repair; DNA-Binding Proteins; Exodeoxyribonucleases; HEK293 Cells; Hepacivirus; Hepatitis C, Chronic; Humans; Ku Autoantigen; RNA Replicase; Viral Nonstructural Proteins; Werner Syndrome Helicase
Publisher
NLM (Medline)
Type
journal article