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Cortical Dynein Drives Centrosome Clustering in Cells with Centrosome Amplification

Dayna L. Mercadante, William A. Aaron, Sarah D. Olson, Amity L. Manning
doi: https://doi.org/10.1101/2022.08.04.502862
Dayna L. Mercadante
1Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
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William A. Aaron
2Department of Mathematical Sciences, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
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Sarah D. Olson
1Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
2Department of Mathematical Sciences, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
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  • For correspondence: sdolson@wpi.edu
Amity L. Manning
1Bioinformatics and Computational Biology Program, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
3Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA
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  • For correspondence: almanning@wpi.edu
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Abstract

During cell division, the microtubule nucleating and organizing organelle, known as the centrosome, is critical for the formation of the mitotic spindle. In cells with two centrosomes, each centrosome functions as an anchor point for microtubules, leading to the formation of a bipolar spindle and progression through a bipolar cell division. When extra centrosomes are present, multipolar spindles form and the parent cell may divide into more than two daughter cells. Cells that are born from multipolar divisions are not viable and hence clustering of extra centrosomes and progression to a bipolar division are critical determinants of viability in cells with extra centrosomes. We combine experimental approaches with computational modeling to define a role for cortical dynein in centrosome clustering. We show that centrosome clustering fails and multipolar spindles dominate when cortical dynein distribution or activity is experimentally perturbed. Our simulations further reveal that centrosome clustering is sensitive to the distribution of dynein on the cortex. Together, these results indicate that dynein’s cortical localization alone is insufficient for effective centrosome clustering and instead, dynamic relocalization of dynein from one side of the cell to the other throughout mitosis promotes timely clustering and bipolar cell division in cells with extra centrosomes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 05, 2022.
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Cortical Dynein Drives Centrosome Clustering in Cells with Centrosome Amplification
Dayna L. Mercadante, William A. Aaron, Sarah D. Olson, Amity L. Manning
bioRxiv 2022.08.04.502862; doi: https://doi.org/10.1101/2022.08.04.502862
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Cortical Dynein Drives Centrosome Clustering in Cells with Centrosome Amplification
Dayna L. Mercadante, William A. Aaron, Sarah D. Olson, Amity L. Manning
bioRxiv 2022.08.04.502862; doi: https://doi.org/10.1101/2022.08.04.502862

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