title: Xeroderma pigmentosum C is involved in Epstein Barr virus DNA replication.
abstract: Cellular mismatch and base-excision repair machineries have been shown to be involved in Epstein-Barr Virus (EBV) lytic DNA replication. We report here that nucleotide-excision repair (NER) may also play an important role in EBV lytic DNA replication. Firstly, the EBV BGLF4 kinase interacts with xeroderma pigmentosum C (XPC), the critical DNA damage-recognition factor of NER, in yeast and in vitro, as demonstrated by yeast two-hybrid and glutathione S-transferase pull-down assays. Simultaneously, XPC was shown, by indirect immunofluorescence and co-immunoprecipitation assays, to interact and colocalize with BGLF4 in EBV-positive NA cells undergoing lytic viral replication. In addition, the efficiency of EBV DNA replication was reduced about 30-40 % by an XPC small interfering RNA. Expression of BGLF4 enhances cellular DNA-repair activity in p53-defective H1299/bcl2 cells in a host-cell reactivation assay. This enhancement was not observed in the XPC-mutant cell line XP4PA-SV unless complemented by ectopic XPC, suggesting that BGLF4 may stimulate DNA repair in an XPC-dependent manner. Overall, we suggest that the interaction of BGLF4 and XPC may be involved in DNA replication and repair and thereby enhance the efficiency of viral DNA replication.
authors.affiliation: Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
authors.forename: Jiin-Tarng
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.affiliation: Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
authors.forename: Mei-Ru
authors.initials: MR
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D004260:DNA Repair; D004261:DNA Replication; D004279:DNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D004268:DNA-Binding Proteins; D014764:Viral Proteins; C086984:XPC protein, human; C406063:BGLF4 protein, Epstein-Barr virus; D017346:Protein Serine-Threonine Kinases