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Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Hepatitis B virus X protein interferes with cellular DNA repair
S A Becker1, T H Lee, J S Butel
1Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Journal of Virology
|January 7, 1998
Summary
Hepatitis B virus X protein (HBx) inhibits DNA repair by binding to XAP-1/UVDDB. This impaired DNA repair by HBx may lead to liver cancer development.
Area of Science:
- Hepatitis B virus research
- Molecular biology
- Cancer research
Background:
- Hepatitis B virus X protein (HBx) is a transactivator linked to liver cancer.
- HBx interacts with cellular proteins, including XAP-1/UVDDB, involved in DNA repair.
Purpose of the Study:
- To determine the minimal domain of HBx required for binding to XAP-1/UVDDB.
- To investigate the effect of HBx-XAP-1/UVDDB interaction on cellular DNA repair capacity.
- To explore the role of impaired DNA repair in HBx-mediated hepatocarcinogenesis.
Main Methods:
- Site-directed mutagenesis to create HBx mutants.
- Assays for nucleotide excision repair (NER) including unscheduled DNA synthesis and host cell reactivation.
- Reporter gene assays to assess HBx transactivation activity.
Main Results:
- The minimal domain of HBx for XAP-1/UVDDB binding was localized to amino acids 55–101.
- HBx expression significantly inhibited cellular DNA repair in two independent assays.
- HBx was expressed at physiologically relevant levels and transactivated reporter genes.
Conclusions:
- HBx interferes with cellular nucleotide excision repair (NER) by binding to XAP-1/UVDDB.
- Impaired DNA repair by HBx may contribute to hepatocarcinogenesis by increasing DNA mutation accumulation.
- This suggests a novel mechanism for viral-associated carcinogenesis via disruption of DNA repair pathways.
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