Abstract
Aurora B kinase is essential for faithful chromosome segregation during mitosis. During (pro)metaphase, Aurora B is concentrated at the inner centromere by the kinases Haspin and Bub1. However, how Haspin and Bub1 collaborate to control Aurora B activity at centromeres remains unclear. Here, we show that either Haspin or Bub1 activity is sufficient to recruit Aurora B to a distinct chromosomal locus. Moreover, we identified a small, Bub1 kinase-dependent Aurora B pool that supported faithful chromosome segregation in otherwise unchallenged cells. Joined inhibition of Haspin and Bub1 activities fully abolished Aurora B accumulation at centromeres. While this impaired the correction of erroneous KT-MT attachments, it did not compromise the mitotic checkpoint, nor the phosphorylation of the Aurora B kinetochore substrates Hec1, Dsn1, and Knl1. This suggests that Aurora B substrates at the kinetochore are not phosphorylated by centromere-localized pools of Aurora B, and calls for a reevaluation of the current spatial models for how tension affects Aurora B-dependent kinetochore phosphorylation.
© 2020 Hadders et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aurora Kinase B / genetics
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Aurora Kinase B / metabolism*
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Chromosomal Proteins, Non-Histone / genetics
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Chromosomal Proteins, Non-Histone / metabolism
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Chromosome Segregation*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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HCT116 Cells
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Kinesins / genetics
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Kinesins / metabolism
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Kinetochores / enzymology*
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M Phase Cell Cycle Checkpoints
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism
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Microtubules / enzymology*
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Microtubules / genetics
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Mitosis*
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Phosphorylation
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Signal Transduction
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Time Factors
Substances
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Chromosomal Proteins, Non-Histone
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Cytoskeletal Proteins
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DSN1 protein, human
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Intracellular Signaling Peptides and Proteins
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KIF2C protein, human
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Knl1 protein, human
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Microtubule-Associated Proteins
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NDC80 protein, human
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AURKB protein, human
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Aurora Kinase B
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BUB1 protein, human
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HASPIN protein, human
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Protein Serine-Threonine Kinases
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Kinesins