Nonautonomous movement of chromosomes in mitosis

Dev Cell. 2013 Oct 14;27(1):60-71. doi: 10.1016/j.devcel.2013.08.004.

Abstract

Kinetochores are the central force-generating machines that move chromosomes during cell division. It is generally assumed that kinetochores move in an autonomous manner. However, we reveal here that movements of neighboring sister-kinetochore pairs in metaphase are correlated in a distance-dependent manner. This correlation increases in the absence of kinetochore oscillations or stable end-on attachments. This suggests that periodic movements of bioriented chromosomes limit the correlated motion of nonsisters. Computer simulations show that these correlated movements can occur when elastic crosslinks are placed between the K-fibers of oscillating kinetochores. Strikingly, inhibition of the microtubule crosslinking motor kinesin-5 Eg5 leads to an increase in nonsister correlation and impairs periodic oscillations. These phenotypes are partially rescued by codepletion of the kinesin-12 Kif15, demonstrating a function for kinesin-5 and kinesin-12 motors in driving chromosome movements, possibly as part of a crosslinking structure that correlates the movements of nonsister kinetochores.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatids / metabolism
  • Chromosome Segregation*
  • Chromosomes, Human / metabolism*
  • HeLa Cells
  • Humans
  • Kinesins / metabolism
  • Kinetochores / metabolism
  • Mitosis / genetics*

Substances

  • KIF11 protein, human
  • KIF15 protein, human
  • Kinesins