Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation
| Autor: | René Holtackers, Mukta Belwal, Samuel Wieser, Ana C. Amaro, Julien Mouysset, Nunu Mchedlishvili, Patrick Meraldi |
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| Rok vydání: | 2012 |
| Předmět: |
Prometaphase
M Phase Cell Cycle Checkpoints Chromosomal Proteins Non-Histone Nuclear Envelope Cell Cycle Proteins Spindle Apparatus Biology Microtubule-Associated Proteins/deficiency/metabolism Microtubules Chromosome segregation 03 medical and health sciences 0302 clinical medicine Microtubule Chromosome Segregation Humans Kinetochores Mitosis Nuclear Envelope/metabolism 030304 developmental biology Centrosome 0303 health sciences Kinetochore Cell Biology Cell biology Cell Cycle Proteins/deficiency/metabolism Centrosome/metabolism Kinetochores/metabolism Microtubules/metabolism Centrosome separation Microtubule-Associated Proteins Mitotic Spindle Apparatus/metabolism 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Journal of Cell Science, Vol. 125, No Pt 4 (2012) pp. 906-18 Journal of cell science |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.091967 |
| Popis: | At the onset of mitosis, cells need to break down their nuclear envelope, form a bipolar spindle and attach the chromosomes to microtubules via kinetochores. Previous studies have shown that spindle bipolarization can occur either before or after nuclear envelope breakdown. In the latter case, early kinetochore–microtubule attachments generate pushing forces that accelerate centrosome separation. However, until now, the physiological relevance of this prometaphase kinetochore pushing force was unknown. We investigated the depletion phenotype of the kinetochore protein CENP-L, which we find to be essential for the stability of kinetochore microtubules, for a homogenous poleward microtubule flux rate and for the kinetochore pushing force. Loss of this force in prometaphase not only delays centrosome separation by 5–6 minutes, it also causes massive chromosome alignment and segregation defects due to the formation of syntelic and merotelic kinetochore–microtubule attachments. By contrast, CENP-L depletion has no impact on mitotic progression in cells that have already separated their centrosomes at nuclear envelope breakdown. We propose that the kinetochore pushing force is an essential safety mechanism that favors amphitelic attachments by ensuring that spindle bipolarization occurs before the formation of the majority of kinetochore–microtubule attachments. |
| Databáze: | OpenAIRE |
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