Lai C.-K.Jeng K.-S.Machida K.Cheng Y.-S.Lai M.M.C.2019-07-222019-07-22200800426822https://scholars.lib.ntu.edu.tw/handle/123456789/414374Hepatitis 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.£^-H2AX fociAtaxia-telangiectasia mutatedDNA repairDouble-strand DNA breaksHepatitis C virusNonstructural protein NS3/4AOncogenesis[SDGs]SDG3journal article10.1016/j.virol.2007.08.037https://www.scopus.com/inward/record.uri?eid=2-s2.0-36549020078&doi=10.1016%2fj.virol.2007.08.037&partnerID=40&md5=811cfbe44b1f4e78c7812bcfe57c4704179316782-s2.0-36549020078https://www.scopus.com/inward/record.uri?eid=2-s2.0-36549020078&doi=10.1016%2fj.virol.2007.08.037&partnerID=40&md5=811cfbe44b1f4e78c7812bcfe57c4704