SUMO Modification of DNA topoisomerase II: Trying to get a CENse of it all

Abstract

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.

Proteome-wide screens for small ubiquitin-like modifier (SUMO) substrates identify Arabidopsis proteins implicated in diverse biological processes

“…6B). Roles for SUMO modification in sister chromatid cohesion, condensation, and topoisomerase functions have been suggested (45,46).In addition to these categories, we also detected significant enrichment in proteins involved in catabolism (observed with both datasets), photosynthesis (yeast two-hybrid; Fig. 6A), and actinand microtubule-based movement (putative substrates identified computationally; Fig.…”

“…6B). Roles for SUMO modification in sister chromatid cohesion, condensation, and topoisomerase functions have been suggested (45,46).…”

SUMO1 in human sperm: new targets, role in motility and morphology and relationship with DNA damage

“…However, the occurrence of PI brighter sperm with co-localisation of the two signals in the nucleus and the demonstration that when DNA fragmentation is induced in mature sperm by freezing and thawing or oxidative insults, also sumoylation increases (Fig. 7), as it occurs in somatic and germ cells (Lee & Bachant 2009, Shrivastava et al 2010, suggests a possible active involvement of this post-translational modification in responses to stressful conditions. It is possible that the increase in sumoylation occurs in an attempt to repair or to limit the damage to DNA.…”

“…The increase in Topoisomerase IIa SUMO1-ylation in sperm following freezing and thawing is not surprising as stressful conditions have been shown to increase the sumoylation of topoisomerases in somatic cells (Lee & Bachant 2009). It should be noted that Topoisomerases II have been shown to express unique properties in sperm, retaining DNA relaxation activity and lacking the decatenation one (Har-Vardi et al 2007).…”

“…This protein is present in the post-acrosomal region of the sperm head, compatible with localisation in the nuclei (Har-Vardi et al 2007), where an intense SUMO1 signal is present . Previous studies demonstrated that Topoisomerase IIa is SUMO2/3-ylated in germ cells during meiosis, localising to centromeric heterochromatin (Shrivastava et al 2010), where it may have a role in sister chromatid separation during cell division as it occurs in somatic cells (Lee & Bachant 2009) and in Xenopus oocytes (Azuma 2009). Thus, sumoylation of Topoisomerase IIa in mature sperm may represent a remnant of spermatogenesis persisting in immature or morphologically altered sperm.…”