Postreplicative mismatch repair factors are recruited to Epstein-Barr virus replication compartments.
The mismatch repair (MMR) system, highly conserved throughout evolution, corrects nucleotide mispairing that arise during cellular DNA replication. We report here that proliferating cell nuclear antigen (PCNA), the clamp loader complex (RF-C), and a series of MMR proteins like MSH-2, MSH-6, MLH1, and hPSM2 can be assembled to Epstein-Barr virus replication compartments, the sites of viral DNA synthesis. Levels of the DNA-bound form of PCNA increased with progression of viral productive replication. Bromodeoxyuridine-labeled chromatin immunodepletion analyses confirmed that PCNA is loaded onto newly synthesized viral DNA as well as BALF2 and BMRF1 viral proteins during lytic replication. Furthermore, the anti-PCNA, -MSH2, -MSH3, or -MSH6 antibodies could immunoprecipitate BMRF1 replication protein probably via the viral DNA genome. PCNA loading might trigger transfer of a series of host MMR proteins to the sites of viral DNA synthesis. The MMR factors might function for the repair of mismatches that arise during viral replication or act to inhibit recombination between moderately divergent (homologous) sequences.
Daikoku
Tohru
T
Division of Virology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Kudoh
Ayumi
A
Sugaya
Yutaka
Y
Iwahori
Satoko
S
Shirata
Noriko
N
Isomura
Hiroki
H
Tsurumi
Tatsuya
T
D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D017209:Apoptosis; D020137:Base Pair Mismatch; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D004261:DNA Replication; D004279:DNA, Viral / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011995:Recombination, Genetic; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral; C096364:BALF2 protein, Human herpesvirus 4; D002352:Carrier Proteins; D002843:Chromatin; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C083204:Epstein-Barr virus early antigen diffuse component; C501485:Mlh1 protein, mouse; C102997:Msh6 protein, mouse; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D014764:Viral Proteins; D004247:DNA; D000251:Adenosine Triphosphatases; C499533:Pms2 protein, mouse; D000070976:Mismatch Repair Endonuclease PMS2; C497173:Msh2 protein, mouse; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes; D001973:Bromodeoxyuridine