SUMO modification of DNA topoisomerase II: trying to get a CENse of it all.

DNA topoisomerase II (topo II) is an essential determinant of chromosome structure and function, acting to resolve topological problems inherent in recombining, transcribing, replicating and segregating DNA. In particular, the unique decatenating activity of topo II is required for sister chromatids to disjoin and separate in mitosis. Topo II exhibits a dynamic localization pattern on mitotic chromosomes, accumulating at centromeres and axial chromosome cores prior to anaphase. In organisms ranging from yeast to humans, a fraction of topo II is targeted for SUMO conjugation in mitotic cells, and here we review our current understanding of the significance of this modification. As we shall see, an emerging consensus is that in metazoans SUMO modification is required for topo II to accumulate at centromeres, and that in the absence of this regulation there is an elevated frequency of chromosome non-disjunction, segregation errors, and aneuploidy. The underlying molecular mechanisms for how SUMO controls topo II are as yet unclear. In closing, however, we will evaluate two possible interpretations: one in which SUMO promotes enzyme turnover, and a second in which SUMO acts as a localization tag for topo II chromosome trafficking.