Recruitment of cdc2 kinase by DNA topoisomerase II is coupled to chromatin remodeling.
Although initiation of chromosome condensation during early prophase is linked 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 coupled to chromatin remodeling. We now report that cdc2 kinase forms stable molecular complexes with the nuclear enzyme DNA topoisomerase II, which is associated with marked stimulation of both DNA binding and catalytic activity 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 have neither endogenous topoisomerase II nor cdc2 kinase. The physical association between the two enzymes alters the DNA/topoisomerase II interaction as shown by pulse-field electrophoresis after incubation of intact nuclei with 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 results reveal a novel property of cyclin-dependent kinases and demonstrate that the recruitment of cdc2 kinase by topoisomerase II is coupled to chromatin remodeling.
Escargueil
A E
AE
Laboratory of Tumor Biology and Pharmacology, CNRS UMR 8532, Institut Gustave Roussy, Villejuif 94805 cedex, France.
Plisov
S Y
SY
Skladanowski
A
A
Borgne
A
A
Meijer
L
L
Gorbsky
G J
GJ
Larsen
A K
AK
D021581:Active Transport, Cell Nucleus; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism* / Q000502:physiology*; D008957:Models, Genetic; D011418:Prophase
D002843:Chromatin; D004247:DNA; D016203:CDC2 Protein Kinase; D004250:DNA Topoisomerases, Type II