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Molecular control of kinetochore-microtubule dynamics and chromosome oscillations
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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. doi:10.1038/ncb2033
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Official URL: http://dx.doi.org/10.1038/ncb2033
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 | ||||
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| Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Microtubules, Chromosomes -- Research | ||||
| Journal or Publication Title: | Nature Cell Biology | ||||
| Publisher: | Nature Publishing Group | ||||
| ISSN: | 1465-7392 | ||||
| Official Date: | April 2010 | ||||
| Dates: |
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| Volume: | Vol.12 | ||||
| Number: | No.4 | ||||
| Number of Pages: | 21 | ||||
| Page Range: | 319-U42 | ||||
| DOI: | 10.1038/ncb2033 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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