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

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Abstract
A subset (γ2) 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 US11, also requires two viral proteins, the α protein infected cell protein (ICP) 22 and the protein kinase UL13. Earlier we showed that UL13 and ICP22 mediate the stabilization of cdc2 and the replacement of its cellular partner, cyclin B, with the viral DNA polymerase processivity factor UL42. Here we report that cdc2 and its new partner, UL42, bind a phosphorylated form of topoisomerase IIα. The posttranslational modification of topoisomerase IIα and its interaction with cdc2–UL42 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 IIα. The intricate manner in which the virus recruits topoisomerase IIα for post-DNA synthesis expression of viral genes suggests that topoisomerase IIα also is required for untangling concatemeric DNA progeny for optimal transcription of late genes.