DNA topoisomerase II (Topo II) is essential for preventing tangling of double-stranded DNA during processes such as replication, recombination and transcription. It also associates with chromosomes at mitosis, but its roles in regulation of mitotic chromosome dynamics are the subject of considerable debate. William Earnshaw, Mar Carmena and co-workers have therefore examined the effect of knocking down Topo II by RNA interference in Drosophila S2 cells (see. p. 4715). Their studies confirm that Topo II is required for sister chromatid separation. It is not needed for kinetochore assembly but does appear to function in chromosome condensation - chromosomes in the knocked down cells are significantly less condensed than they should be. Perhaps the most interesting effect of knocking down Topo II, however, is on chromosomes aligned at the metaphase plate: their arms frequently protrude out towards the spindle poles, while the kinetochores remain at the plate. This suggests that Topo II has previously unexpected functions in chromosome dynamics and might even separate DNA from other molecules with which it becomes entangled.