Molecular control of kinetochore-microtubule dynamics and chromosome oscillations
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 1465-7392Full text not available from this repository.
Official URL: http://dx.doi.org/10.1038/ncb2033
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 Sciences > Cell & Developmental 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|
|Official Date:||April 2010|
|Number of Pages:||21|
|Access rights to Published version:||Restricted or Subscription Access|
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