Cdk1 phosphorylation of the kinetochore protein Nsk1 prevents error-prone chromosome segregation
| Autor: | Melanie D. Ohi, Kevin M. Creamer, Janet F. Partridge, Ryoma Ohi, Kathleen L. Gould, Lucy X. Lu, Jun-Song Chen, Chauca A. English |
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| Rok vydání: | 2011 |
| Předmět: |
Saccharomyces cerevisiae Proteins
Dynein Mitosis Cell Cycle Proteins Saccharomyces cerevisiae Spindle Apparatus Biology environment and public health Microtubules Chromosome segregation 03 medical and health sciences 0302 clinical medicine Microtubule Chromosome Segregation Report CDC2 Protein Kinase Centromere Phosphorylation Kinetochores Research Articles 030304 developmental biology 0303 health sciences Kinetochore Dyneins Cell Biology Spindle apparatus Cell biology enzymes and coenzymes (carbohydrates) Spindle localization biological phenomena cell phenomena and immunity Chromosomes Fungal 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Phosphorylation of the kinetochore component Nsk1 by Cdk1 antagonizes its localization to and function at the kinetochore and spindle during early mitosis. Cdk1 controls many aspects of mitotic chromosome behavior and spindle microtubule (MT) dynamics to ensure accurate chromosome segregation. In this paper, we characterize a new kinetochore substrate of fission yeast Cdk1, Nsk1, which promotes proper kinetochore–MT (k-MT) interactions and chromosome movements in a phosphoregulated manner. Cdk1 phosphorylation of Nsk1 antagonizes Nsk1 kinetochore and spindle localization during early mitosis. A nonphosphorylatable Nsk1 mutant binds prematurely to kinetochores and spindle, cementing improper k-MT attachments and leading to high rates of lagging chromosomes that missegregate. Accordingly, cells lacking nsk1 exhibit synthetic growth defects with mutations that disturb MT dynamics and/or kinetochore structure, and lack of proper phosphoregulation leads to even more severe defects. Intriguingly, Nsk1 is stabilized by binding directly to the dynein light chain Dlc1 independently of the dynein motor, and Nsk1–Dlc1 forms chainlike structures in vitro. Our findings establish new roles for Cdk1 and the Nsk1–Dlc1 complex in regulating the k-MT interface and chromosome segregation. |
| Databáze: | OpenAIRE |
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