Hepatitis B virus X protein does not influence essential steps of nucleotide excision repair effected by human liver extracts.
The X protein (HBx) of hepatitis B virus (HBV) is thought to compromise TFIIH function during hepatocyte nucleotide excision repair (NER) to cause the accumulation of hepatocarcinogenic mutations. The TFIIH holoenzyme, including XPB and XPD helicases, is absolutely required for transcription coupled (TCR) as well as global genome (GGR) NER pathways. Using an assay in which GGR carried out by extracts of foetal hepatocytes is reconstituted, we found that incisions [Formula: see text] and [Formula: see text] to a defined cisplatin DNA lesion occurred normally in the presence of functional recombinant HBx. Moreover, HBx did not significantly impair synthesis of the repair patch that completes the NER pathway. These data indicate that HBx does not directly interrupt the function of TFIIH during GGR and suggest that any HBx-mediated inhibitory effect on TFIIH is a transcription-coupled event.
Capovilla
Alexio
A
Hepatitis B Virus Research Programme, Department of Molecular Medicine and Haematology, University of the Witwatersrand, Private Bag 3, Wits 2050, South Africa.
Arbuthnot
Patrick
P
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000196:embryology / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D051758:Transcription Factor TFIIH; D019473:Transcription Factors, TFII / Q000737:chemistry* / Q000378:metabolism; D015533:Transcriptional Activation; D017361:Viral Nonstructural Proteins / Q000737:chemistry*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C110719:LAMTOR5 protein, human; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D019473:Transcription Factors, TFII; D017361:Viral Nonstructural Proteins; D051758:Transcription Factor TFIIH; D004247:DNA