Author: ["Ana C. Amaro","Catarina P. Samora","René Holtackers","Enxiu Wang","Isabel J. Kingston","Maria Alonso","Michael Lampson","Andrew D. McAinsh","Patrick Meraldi"]
CITE.CC academic search helps you expand the influence of your papers.
Abstract
The core kinetochore protein CENP-H is shown to be required for the organization of the metaphase plate. CENP-H regulates microtubule plus-end dynamics, and chromosome oscillations, which are shown to be essential for chromosome congression. 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.Cite this article
Amaro, A., Samora, C., Holtackers, R. et al. Molecular control of kinetochore-microtubule dynamics and chromosome oscillations. Nat Cell Biol 12, 319–329 (2010). https://doi.org/10.1038/ncb2033 