Amaro, Ana C., Samora, Catarina P., Holtackers, Rene, Wang, Enxiu, Kingston, Isabel J., Alonso, M. (Maria), Lampson, Michael, McAinsh, Andrew D. and Meraldi, Patrick. (2010) Molecular control of kinetochore-microtubule dynamics and chromosome oscillations. Nature Cell Biology, Vol.12 (No.4). 319-U42. ISSN 1465-7392

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Abstract

Chromosome segregation in metazoans requires the alignment of sister kinetochores on the metaphase plate. During chromosome alignment, bioriented kinetochores move chromosomes by regulating the plus-end dynamics of the attached microtubules. The bundles of kinetochore-bound microtubules alternate between growth and shrinkage, leading to regular oscillations along the spindle axis. However, the molecular mechanisms that coordinate microtubule plus-end dynamics remain unknown. Here we show that centromere protein (CENP)-H, a subunit of the CENP-A nucleosome-associated and CENP-A distal complexes (CENP-A NAC/CAD), is essential for this coordination, because kinetochores lacking CENP-H establish bioriented attachments but fail to generate regular oscillations, as a result of an uncontrolled rate of microtubule plus-end turnover. These alterations lead to rapid erratic movements that disrupt metaphase plate organization. We also show that the abundance of the CENP-A NAC/CAD subunits CENP-H and CENP-I dynamically change on individual sister kinetochores in vivo, because they preferentially bind the sister kinetochore attached to growing microtubules, and that one other subunit, CENP-Q, binds microtubules in vitro. We therefore propose that CENP-A NAC/CAD is a direct regulator of kinetochore-microtubule dynamics, which physically links centromeric DNA to microtubule plus ends.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Cell Biology Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Microtubules, Chromosomes -- Research
Journal or Publication Title:	Nature Cell Biology
Publisher:	Nature Publishing Group
ISSN:	1465-7392
Date:	April 2010
Volume:	Vol.12
Number:	No.4
Number of Pages:	21
Page Range:	319-U42
Identification Number:	10.1038/ncb2033
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/6149

Data sourced from Thomson Reuters' Web of Knowledge

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