Topoisomerase II SUMOylation activates a metaphase checkpoint via Haspin and Aurora B kinases

Nootan Pandey, Daniel Keifenheim, Makoto Michael Yoshida, Victoria A. Hassebroek, Caitlin Soroka, Yoshiaki Azuma, Duncan J. Clarke

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Topoisomerase II (Topo II) is essential for mitosis since it resolves sister chromatid catenations. Topo II dysfunction promotes aneuploidy and drives cancer. To protect from aneuploidy, cells possess mechanisms to delay anaphase onset when Topo II is perturbed, providing additional time for decatenation. Molecular insight into this checkpoint is lacking. Here we present evidence that catalytic inhibition of Topo II, which activates the checkpoint, leads to SUMOylation of the Topo II C-terminal domain (CTD). This modification triggers mobilization of Aurora B kinase from inner centromeres to kinetochore proximal centromeres and the core of chromosome arms. Aurora B recruitment accompanies histone H3 threonine-3 phosphorylation and requires Haspin kinase. Strikingly, activation of the checkpoint depends both on Haspin and Aurora B. Moreover, mutation of the conserved CTD SUMOylation sites perturbs Aurora B recruitment and checkpoint activation. The data indicate that SUMOylated Topo II recruits Aurora B to ectopic sites, constituting the molecular trigger of the metaphase checkpoint when Topo II is catalytically inhibited.

Original languageEnglish (US)
JournalThe Journal of cell biology
Issue number1
StatePublished - Jan 6 2020

Bibliographical note

Funding Information:
This study was funded by National Institutes of Health grants R01GM112793 and R01GM130858; the University of Minnesota Foundation; the University of Minnesota Office of the Vice President for Research; and University of Kansas Strategic Initiative Grant (INS0073115). The authors declare no competing financial interests.

Publisher Copyright:
© 2019 Pandey et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural


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