Regulation of kinetochore-microtubule attachments through homeostatic control during mitosis

Nat Rev Mol Cell Biol. 2015 Jan;16(1):57-64. doi: 10.1038/nrm3916. Epub 2014 Dec 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomal Instability*
  • Chromosome Segregation*
  • Humans
  • Kinetochores / metabolism*
  • Microtubules / genetics
  • Microtubules / metabolism*
  • Mitosis*
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology