Maturation of the kinetochore-microtubule interface and the meaning of metaphase

Chromosome Res. 2012 Jul;20(5):563-77. doi: 10.1007/s10577-012-9298-8.


Chromosome positioning at the equator of the mitotic spindle emerges out of a relatively entropic background. At this moment, termed metaphase, all kinetochores have typically captured microtubules leading to satisfaction of the spindle-assembly checkpoint, but the cell does not enter anaphase immediately. The waiting time in metaphase is related to the kinetics of securin and cyclin B1 degradation, which trigger sister-chromatid separation and promote anaphase processivity, respectively. Yet, as judged by metaphase duration, such kinetics vary widely between cell types and organisms, with no evident correlation to ploidy or cell size. During metaphase, many animal and plant spindles are also characterized by a conspicuous "flux" activity characterized by continuous poleward translocation of spindle microtubules, which maintain steady-state length and position. Whether spindle microtubule flux plays a specific role during metaphase remains arguable. Based on known experimental parameters, we have performed a comparative analysis amongst different cell types from different organisms and show that spindle length, metaphase duration and flux velocity combine within each system to obey a quasi-universal rule. As so, knowledge of two of these parameters is enough to estimate the third. This trend indicates that metaphase duration is tuned to allow approximately one kinetochore-to-pole round of microtubule flux. We propose that the time cells spend in metaphase evolved as a quality enhancement step that allows for the uniform stabilization/correction of kinetochore-microtubule attachments, thereby promoting mitotic fidelity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Chromosome Segregation
  • Chromosomes / metabolism
  • Chromosomes / physiology
  • Cytokinesis
  • Humans
  • Kinetochores / metabolism*
  • Kinetochores / physiology
  • M Phase Cell Cycle Checkpoints
  • Metaphase*
  • Microtubules / metabolism*
  • Microtubules / physiology
  • Mitosis
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology
  • Time Factors