https://scholars.lib.ntu.edu.tw/handle/123456789/414374
Title: | Hepatitis C virus NS3/4A protein interacts with ATM, impairs DNA repair and enhances sensitivity to ionizing radiation | Authors: | Lai C.-K. Jeng K.-S. Machida K. Cheng Y.-S. Lai M.M.C. |
Keywords: | £^-H2AX foci;Ataxia-telangiectasia mutated;DNA repair;Double-strand DNA breaks;Hepatitis C virus;Nonstructural protein NS3/4A;Oncogenesis | Issue Date: | 2008 | Journal Volume: | 370 | Journal Issue: | 2 | Start page/Pages: | 295-309 | Source: | Virology | Abstract: | Hepatitis C virus (HCV) infection is frequently associated with the development of hepatocellular carcinomas and non-Hodgkin's B-cell lymphomas. Nonstructural protein 3 (NS3) of HCV possesses serine protease, nucleoside triphosphatase, and helicase activities, while NS4A functions as a cofactor for the NS3 serine protease. Here, we show that HCV NS3/4A interacts with the ATM (ataxia-telangiectasia mutated), a cellular protein essential for cellular response to irradiation. The expression of NS3/4A caused cytoplasmic translocation of either endogenous or exogenous ATM and delayed dephosphorylation of the phosphorylated ATM and £^-H2AX following ionizing irradiation. As a result, the irradiation-induced £^-H2AX foci persisted longer in the NS3/4A-expressing cells. Furthermore, these cells showed increased comet tail moment in single-cell electrophoresis assay, indicating increased double-strand DNA breaks. The cells harboring an HCV replicon also exhibited cytoplasmic localization of ATM and increased sensitivity to irradiation. These results demonstrate that NS3/4A impairs the efficiency of DNA repair by interacting with ATM and renders the cells more sensitive to DNA damage. This effect may contribute to HCV oncogenesis. ? 2007 Elsevier Inc. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/414374 | ISSN: | 00426822 | DOI: | 10.1016/j.virol.2007.08.037 https://www.scopus.com/inward/record.uri?eid=2-s2.0-36549020078&doi=10.1016%2fj.virol.2007.08.037&partnerID=40&md5=811cfbe44b1f4e78c7812bcfe57c4704 |
Appears in Collections: | 植物科學研究所 |
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1-s2.0-S0042682207005661-main.pdf | 2.19 MB | Adobe PDF | View/Open |
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