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.
| Original language | English |
|---|---|
| Article number | e201907087 |
| Number of pages | 27 |
| Journal | Journal of Cell Biology |
| Volume | 219 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2 Mar 2020 |
Keywords
- Aurora Kinase B/genetics
- Chromosomal Proteins, Non-Histone/genetics
- Chromosome Segregation
- Cytoskeletal Proteins/genetics
- HCT116 Cells
- Humans
- Intracellular Signaling Peptides and Proteins/genetics
- Kinesin/genetics
- Kinetochores/enzymology
- M Phase Cell Cycle Checkpoints
- Microtubule-Associated Proteins/genetics
- Microtubules/enzymology
- Mitosis
- Phosphorylation
- Protein-Serine-Threonine Kinases/genetics
- Signal Transduction
- Time Factors
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