Localization of p53, retinoblastoma and host replication proteins at sites of viral replication in herpes-infected cells.
Replication of DNA occurs at discrete sites in eukaryotic cell nuclei, where replication proteins are clustered into large complexes, or 'replicases'. Similarly, viral DNA replication is a highly structured process, notably in herpes simplex virus type-1 (HSV-1; reviewed in ref. 4) in which large globular 'replication compartments' containing the viral replication machinery exist. Replicating cellular DNA redistributes to these compartments upon HSV-1 infection. We have now used antibodies raised against several cellular proteins to detect changes in their subnuclear localization on HSV-1 infection. We found that various proteins involved in cellular DNA replication move to sites of viral DNA synthesis, whereas a selection of non-replication proteins do not. The retinoblastoma protein and p53 (the products of two putative anti-oncogenes) relocate to the same sites as known DNA replication proteins, suggesting that they may be associated with DNA replication complexes in normal, uninfected cells.
Wilcock
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Imperial Cancer Research Fund, Clare Hall Laboratories, Hertfordshire, UK.
Lane
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D000818:Animals; D002451:Cell Compartmentation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein / Q000378:metabolism*; D018139:Simplexvirus / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D004268:DNA-Binding Proteins; C045462:ICP8 protein, Simplexvirus; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D014764:Viral Proteins; D010746:Phosphonoacetic Acid