title: Herpes simplex virus 1 activates cdc2 to recruit topoisomerase II alpha for post-DNA synthesis expression of late genes.
abstract: A subset (gamma(2)) of late herpes simplex virus 1 genes depends on viral DNA synthesis for its expression. For optimal expression, a small number of these genes, exemplified by U(S)11, also requires two viral proteins, the alpha protein infected cell protein (ICP) 22 and the protein kinase U(L)13. Earlier we showed that U(L)13 and ICP22 mediate the stabilization of cdc2 and the replacement of its cellular partner, cyclin B, with the viral DNA polymerase processivity factor U(L)42. Here we report that cdc2 and its new partner, U(L)42, bind a phosphorylated form of topoisomerase II alpha. The posttranslational modification of topoisomerase II alpha and its interaction with cdc2-U(L)42 proteins depend on ICP22 in infected cells. Although topoisomerase II is required for viral DNA synthesis, ICP22 is not, indicating a second function for topoisomerase II alpha. The intricate manner in which the virus recruits topoisomerase II alpha for post-DNA synthesis expression of viral genes suggests that topoisomerase II alpha also is required for untangling concatemeric DNA progeny for optimal transcription of late genes.
authors.affiliation: The Marjorie B. Kovler Viral Oncology Laboratories and Department of Radiation and Cellular Oncology, 910 East 58th Street, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sunil J
authors.initials: SJ
authors.lastname: Advani
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Weichselbaum
authors.forename: Bernard
authors.initials: B
authors.lastname: Roizman
mesh_terms: D000951:Antigens, Neoplasm; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002460:Cell Line; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism*; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D015870:Gene Expression; D005814:Genes, Viral; D006561:Herpes Simplex / Q000378:metabolism / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D008954:Models, Biological; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000951:Antigens, Neoplasm; D004279:DNA, Viral; D004268:DNA-Binding Proteins; C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C078424:EUS1 protein, Equine herpesvirus 1; D011494:Protein Kinases; C082380:UL13 protein, Simplexvirus; D016203:CDC2 Protein Kinase; D004250:DNA Topoisomerases, Type II