Toso, Alberto, Winter, Jennifer R., Garrod, Ainslie J., Amaro, Ana C., Meraldi, Patrick and McAinsh, Andrew D.. (2009) Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly. Journal of Cell Biology, Vol.184 (No.3). pp. 365-372. ISSN 0021-9525

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Abstract

In animal somatic cells, bipolar spindle formation requires separation of the centrosome-based spindle poles. Centrosome separation relies on multiple pathways, including cortical forces and antiparallel microtubule (MT) sliding, which are two activities controlled by the protein kinase aurora A. We previously found that depletion of the human kinetochore protein Mcm21RCENP-O results in monopolar spindles, raising the question as to whether kinetochores contribute to centrosome separation. In this study, we demonstrate that kinetochores promote centrosome separation after nuclear envelope breakdown by exerting a pushing force on the kinetochore fibers (k-fibers), which are bundles of MTs that connect kinetochores to centrosomes. This force is based on poleward MT flux, which incorporates new tubulin subunits at the plus ends of k-fibers and requires stable k-fibers to drive centrosomes apart. This kinetochore-dependent force becomes essential for centrosome separation if aurora A is inhibited. We conclude that two mechanisms control centrosome separation during prometaphase: an aurora A–dependent pathway and a kinetochore-dependent pathway that relies on k-fiber–generated pushing forces.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Cell Biology Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Centrosomes, Chromosomal proteins, Microtubules, Chromosome replication
Journal or Publication Title:	Journal of Cell Biology
Publisher:	Rockefeller University Press
ISSN:	0021-9525
Date:	9 February 2009
Volume:	Vol.184
Number:	No.3
Page Range:	pp. 365-372
Identification Number:	10.1083/jcb.200809055
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Marie Curie Cancer Care, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung [Swiss National Science Foundation] (SNSF), European Science Foundation (ESF)
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URI:	http://wrap.warwick.ac.uk/id/eprint/36496

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