Hepatitis B Virus X Protein Impedes the DNA Repair Via Its Association with Transcription Factor, TFIIH

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2011 Mar 8

PMID 21375739

Citations 25

Authors

Ishtiaq Qadri

Kaneez Fatima

Hany Abdel-Hafiz

Affiliations

Soon will be listed here.

Abstract

Background: Hepatitis B virus (HBV) infections play an important role in the development of hepatocellular carcinoma (HCC). HBV X protein (HBx) is a multifunctional protein that can modulate various cellular processes and plays a crucial role in the pathogenesis of HCC. HBx is known to interact with DNA helicase components of TFIIH, a basal transcriptional factor and an integral component of DNA excision repair.

Results: In this study, the functional relevance of this association was further investigated in the context to DNA repair. By site-directed mutagenesis HBx's critical residues for interaction with TFIIH were identified. Similarly, TFIIH mutants lacking ATPase domain and the conserved carboxyl-terminal domain failed to interact with HBx. Yeast and mammalian cells expressing HBx(wt) conferred hypersensitivity to UV irradiation, which is interpreted as a basic deficiency in nucleotide excision repair. HBx(mut120) (Glu to Val) was defective in binding to TFIIH and failed to respond to UV.

Conclusions: We conclude that HBx may act as the promoting factor by inhibiting DNA repair causing DNA damage and accumulation of errors, thereby contributing to HCC development.

Citing Articles

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