Novel PARP1 binding motif in hepatitis B virus core promoter impairs DNA damage repair.

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Hepatology. 2011 Jun 30. doi: 10.1002/hep.24502. [Epub ahead of print]

Novel PARP1 binding motif in hepatitis B virus core promoter impairs DNA damage

repair.

Hui KL, Ee Chee R.

Source

Singapore Immunology Network, A*STAR, 8A Biomedical Grove, Immunos, Singapore

138648.

Abstract

It is well-established that hepatitis B virus (HBV) infection is associated with

the development of hepatocellular carcinoma (HCC) but patients with high viral

DNA load have significantly higher risk. As host factors are required for

efficient viral replication and may therefore contribute to high viral DNA load,

we screened for host factors that can transcriptionally activate the HBV core

promoter (HBVCP). We report here that poly (ADP-ribose) polymerase 1 (PARP1)

which is known for its DNA repair activity binds prominently to an octamer motif

in the HBVCP and increases transcriptional efficiency. By utilizing a series of

single base substitutions at each nucleotide position of the octamer, the PARP1

binding motif can be defined as " RNNWCAAA " . Intriguingly, introduction of a

vector construct bearing tandem repeats of the octamer motif was able to impair

the DNA repair function of PARP1. This finding suggests that HBV viral DNA

contains specific sequence motifs that may play a role in disrupting the DNA

repair pathways of infected hepatocytes. CONCLUSION: This study has identified a

novel octamer motif in the HBVCP which binds PARP1, and this interaction

increases the replication efficiency of HBV. The presence of this octamer motif

in hepatocytes was shown to inhibit the DNA repair capacity of PARP1,

potentially contributing to the development of HCC. (HEPATOLOGY 2011.).

Copyright © 2011 American Association for the Study of Liver Diseases.

PMID: 21721027 [PubMed - as supplied by publisher]