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dc.contributor.authorPandey, Nootan
dc.contributor.authorKeifenheim, Daniel
dc.contributor.authorYoshida, Makoto Michael
dc.contributor.authorHassebroek, Victoria A.
dc.contributor.authorSoroka, Caitlin
dc.contributor.authorAzuma, Yoshiaki
dc.contributor.authorClarke, Duncan J.
dc.identifier.citationNootan Pandey, Daniel Keifenheim, Makoto Michael Yoshida, Victoria A. Hassebroek, Caitlin Soroka, Yoshiaki Azuma, Duncan J. Clarke; Topoisomerase II SUMOylation activates a metaphase checkpoint via Haspin and Aurora B kinases. J Cell Biol 6 January 2020; 219 (1): e201807189. doi:
dc.descriptionThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.en_US
dc.description.abstractTopoisomerase 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.en_US
dc.publisherRockefeller University Pressen_US
dc.rights© 2019 Pandey et al.en_US
dc.subjectCell cycle and divisionen_US
dc.subjectChromatin or epigeneticsen_US
dc.titleTopoisomerase II SUMOylation activates a metaphase checkpoint via Haspin and Aurora B kinasesen_US
kusw.kuauthorAzuma, Yoshiaki
kusw.kudepartmentMolecular Biosciencesen_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US

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© 2019 Pandey et al.
Except where otherwise noted, this item's license is described as: © 2019 Pandey et al.