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BMC Microbiol. 2011 Mar 4;11:48. doi: 10.1186/1471-2180-11-48.

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

Author information

1
NUST Center of Virology and Immunology, National University of Science and Technology, Academic Block, Kashmir Highway, H-12 Islamabad, Pakistan. ishtiaq80262@yahoo.com

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.

PMID:
21375739
PMCID:
PMC3060106
DOI:
10.1186/1471-2180-11-48
[Indexed for MEDLINE]
Free PMC Article

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