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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...

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Detalles Bibliográficos
Autores principales: Qadri, Ishtiaq, Fatima, Kaneez, AbdeL-Hafiz, Hany
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060106/
https://www.ncbi.nlm.nih.gov/pubmed/21375739
http://dx.doi.org/10.1186/1471-2180-11-48
Descripción
Sumario: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.