HEPATITIS-B VIRUS X-PROTEIN BINDS DAMAGED DNA AND SENSITIZES LIVER-CELLS TO ULTRAVIOLET-IRRADIATION

The mechanism which is responsible for the association of chronic hepa titis B virus (HBV) infection with hepatocellular carcinoma (HCC) is p oorly understood. The protein encoded by the HBV X-gene (HBx) has been identified as potentially oncogenic. HBx is a promiscuous indirect tr ans-activator of a wide range of cellular and viral cis-elements and m ay disrupt the maintenance of genomic integrity by inhibiting p53 func tion and binding a putative DNA repair protein (XAP-1). In this report , we show that there is preferential binding of recombinant HBx to dam aged DNA through an association with nuclear proteins. We have used th e transcriptional acivation by HBx of the beta-actin promoter of a bet a-galactosidase reporter cassette to label cultured Chang liver cells expressing HBx. We demonstrate that cells expressing HBx are sensitise d to the lethal effects of low dose ultraviolet irradiation. These dat a indicate that HBx interferes with liver cell DNA repair by binding d amaged DNA and may predispose to the accumulation of potentially letha l or carcinogenic mutations. (C) 1997 Academic Press.