Loss of kinesin-14 results in aneuploidy via kinesin-5-dependent microtubule protrusions leading to chromosome cut

Nat Commun. 2015 Jun 2;6:7322. doi: 10.1038/ncomms8322.

Abstract

Aneuploidy-chromosome instability leading to incorrect chromosome number in dividing cells-can arise from defects in centrosome duplication, bipolar spindle formation, kinetochore-microtubule attachment, chromatid cohesion, mitotic checkpoint monitoring or cytokinesis. As most tumours show some degree of aneuploidy, mechanistic understanding of these pathways has been an intense area of research, to provide potential therapeutics. Here we present a mechanism for aneuploidy in fission yeast based on spindle pole microtubule defocusing by loss of kinesin-14 Pkl1, leading to kinesin-5 Cut7-dependent aberrant long spindle microtubule minus-end protrusions that push the properly segregated chromosomes to the site of cell division, resulting in chromosome cut at cytokinesis. Pkl1 localization and function at the spindle pole is mutually dependent on spindle pole-associated protein Msd1. This mechanism of aneuploidy bypasses the known spindle assembly checkpoint that monitors chromosome segregation.

Publication types

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

MeSH terms

  • Aneuploidy*
  • Chromosomal Instability*
  • Chromosome Segregation
  • Chromosomes / metabolism*
  • Kinesin / genetics*
  • Kinesin / metabolism*
  • Microtubules / metabolism*
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins / genetics*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Spindle Apparatus
  • Spindle Poles / metabolism*

Substances

  • Cut7 protein, S pombe
  • PKL1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Kinesin