Topoisomerase II: untangling its contribution at the centromere

Abstract

Topoisomerase II (topo II) is a major component of mitotic chromosomes and its unique decatenating activity has been implicated in many aspects of chromosome dynamics including DNA replication, transcription, recombination, chromosome condensation and segregation. Of these, chromosome segregation is the most seriously affected by loss of topo II expression or activity in living cells, most likely because of residual catenations between sister chromatids. At metaphase, vertebrate chromatids are attached to each other principally through their centromeric regions, and we review here evidence that topo II has a specific role at the centromere. Despite strong evidence for the centromere-specific accumulation of topo II protein and the cytogenetic and molecular mapping of topo II catalytic activity to active centromeres, there is so far relatively little evidence for an overt role in centromere function (as judged by the effects of topo II inactivation on kinetochore assembly, bipolar microtubule attachment and chromosome separation). Nevertheless, recent data linking the post-translational modification of topo II to the regulation of sister centromere cohesion suggest that topo II may indeed contribute to the timely separation of centromeres at anaphase.