Projects per year
Abstract
Kinetochores form the interface between chromosomes and spindle microtubules and are thus under tight control by a complex regulatory circuitry. The Aurora B kinase plays a central role within this circuitry by destabilizing improper kinetochore-microtubule attachments and relaying the attachment status to the spindle assembly checkpoint. Intriguingly, Aurora B is conserved even in kinetoplastids, a group of early-branching eukaryotes which possess a unique set of kinetochore proteins. It remains unclear how their kinetochores are regulated to ensure faithful chromosome segregation. Here, we show in Trypanosoma brucei that Aurora B activity controls the metaphase-to-anaphase transition through phosphorylation of the divergent Bub1-like protein KKT14. Depletion of KKT14 overrides the metaphase arrest resulting from Aurora B inhibition, while expression of non-phosphorylatable KKT14 delays anaphase onset. Finally, we demonstrate that re-targeting Aurora B to the outer kinetochore suffices to promote mitotic exit but causes extensive chromosome missegregation in anaphase. Our results indicate that Aurora B and KKT14 are involved in an unconventional circuitry controlling cell cycle progression in trypanosomes.
Original language | English |
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Article number | e202401169 |
Number of pages | 25 |
Journal | Journal of Cell Biology |
Volume | 223 |
Issue number | 11 |
DOIs | |
Publication status | Published - 28 Aug 2024 |
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Understanding the mechanism of chromosome segregation in the kinetoplastid parasite Trypanosoma brucei
1/01/24 → 31/12/31
Project: Research
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Understanding unconventional kinetoplastid kinetochores in Trypanosoma brucei
1/03/23 → 31/12/23
Project: Research
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