Herpes simplex virus 1 activates cdc2 to recruit topoisomerase IIα for post-DNA synthesis expression of late genes

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 a 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, UL42, bind a phosphorylated form of topoisomerase IIalpha. The posttranslational modification of topoisomerase IIalpha and its interaction with cdc2-U(L)42 proteins depend on ICP22 in infected cells. Although topoisomerase 11 is required for viral DNA synthesis, ICP22 is not, indicating a second function for topoisomerase IIalpha. The intricate manner in which the virus recruits topoisomerase IIalpha for post-DNA synthesis expression of viral genes suggests that topoisomerase IIalpha also is required for untangling concatemeric DNA progeny for optimal transcription of late genes.