Hepatitis B virus X protein impedes the DNA repair via its association with transcription factor, TFIIH

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.