Abstract
Faithful chromosome segregation during mitosis is essential for genome integrity and is mediated by the bi-oriented attachment of replicated chromosomes to spindle microtubules through kinetochores. Errors in kinetochore–microtubule (k–MT) attachment that could cause chromosome mis-segregation are frequent and are corrected by the dynamic turnover of k–MT attachments. Thus, regulating the rate of spindle microtubule attachment and detachment to kinetochores is crucial for mitotic fidelity and is frequently disrupted in cancer cells displaying chromosomal instability. A model based on homeostatic principles involving receptors, a core control network, effectors and feedback control may explain the precise regulation of k–MT attachment stability during mitotic progression to ensure error-free mitosis.
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Acknowledgements
The authors thank members of the laboratory for their input and feedback on the manuscript. This work was supported by grants from the US National Institutes of Health (GM51542 to D.A.C and GM008704 to L.K.) and the American Cancer Society (PF-12-103-01-CCG to K.M.G.)
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Godek, K., Kabeche, L. & Compton, D. Regulation of kinetochore–microtubule attachments through homeostatic control during mitosis. Nat Rev Mol Cell Biol 16, 57–64 (2015). https://doi.org/10.1038/nrm3916
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DOI: https://doi.org/10.1038/nrm3916
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