Recruitment of cdc2 kinase by DNA topoisomerase II is coupled to chromatinremodeling

Although initiation of chromosome condensation during early prophase is lin ked temporally to the appearance of the mitotic cdc2 kinase in the nucleus, it is not known what targets the kinase to the nucleus and how this is cou pled to chromatin remodeling. We now report that cdc2 kinase forms stable m olecular complexes with the nuclear enzyme DNA topoisomerase II, which is a ssociated with marked stimulation of both DNA binding and catalytic activit y of topoisomerase II, albeit in a phosphorylation-independent manner. The molecular interaction is required for recruitment of cdc2 kinase, as shown by incubation of purified enzymes with chicken erythrocyte nuclei, which ha ve neither endogenous topoisomerase II nor cdc2 kinase. The physical associ ation between the two enzymes alters the DNA/topoisomerase II interaction a s shown by pulse-field electrophoresis after incubation of intact nuclei wi th the specific topoisomerase II inhibitor VM-26. Furthermore, the presence of both enzymes, but not either enzyme alone, is accompanied by extensive chromatin remodeling converting the interphase nuclei into precondensation chromosomes with striking resemblance to early prophase structures. Our res ults reveal a novel property of cyclin-dependent kinases and demonstrate th at the recruitment of cdc2 kinase by topoisomerase II is coupled to chromat in remodeling.