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bioRxiv · 10.1101/2024.09.29.614573

Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression

Vukusic, K.·Tolic, I. M.
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Abstract

Chromosome congression is crucial for accurate cell division, with key roles played by kinetochore components CENP-E/kinesin-7 and Aurora B kinase. However, Aurora kinases both inhibit and promote congression, suggesting the presence of a larger signaling network. Our study demonstrates that centrosomes inhibit congression initiation when CENP-E is inactive by regulating the activity of kinetochore components. Depleting centrioles via Plk4 inhibition allows chromosomes near acentriolar poles to initiate congression independently of CENP-E. At centriolar poles high Aurora A enhances Aurora B activity, increasing phosphorylation of microtubule-binding proteins at kinetochores and preventing stable microtubule attachments in the absence of CENP-E. Conversely, inhibiting Aurora A or expressing a dephosphorylatable Hec1 mutant enables congression initiation without CENP-E. We propose a self-limiting feedback mechanism involving Aurora kinases and CENP-E that regulates the timing of chromosome movement by modulating kinetochore-microtubule attachments and fibrous corona expansion, with Aurora A activity gradient providing critical spatial cues for the networks function.

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Vukusic, K., Tolic, I. M.. 2024-10-01. Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression. https://doi.org/10.1101/2024.09.29.614573

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