Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis
Kristina M Godek1, Lilian Kabeche1, Duane A Compton1
1Department of Biochemistry, The Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire 03755, USA, and at the Norris Cotton Cancer Center, Lebanon, New Hampshire 03766, USA.
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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