Xeroderma pigmentosum C is involved in Epstein Barr virus DNA replication.
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.
Lu
Chih-Chung
CC
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
Chen
Yi-Chun
YC
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
Wang
Jiin-Tarng
JT
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
Yang
Pei-Wen
PW
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
Chen
Mei-Ru
MR
Graduate Institute and Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan 100, PR China.
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
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