Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase

J Cell Biol. 2019 Apr 1;218(4):1148-1163. doi: 10.1083/jcb.201807228. Epub 2019 Feb 7.

Abstract

Chromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness is not understood. Normal mammalian somatic cells lacking KIF18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo. These defects slow cell proliferation and are associated with impaired postnatal growth and survival in mice. Our studies support a model in which the alignment of mitotic chromosomes promotes proper organization of chromosomes into a single nucleus and continued proliferation by ensuring that chromosomes segregate as a compact mass during anaphase.

Publication types

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

MeSH terms

  • Anaphase*
  • Animals
  • Cell Line
  • Cell Proliferation
  • Chromosome Segregation*
  • Chromosomes, Human*
  • Epithelial Cells / physiology
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mice, Knockout
  • Retinal Pigment Epithelium / physiology
  • Spindle Apparatus / genetics
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / physiology*
  • Time Factors
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • KIF18a protein, mouse
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • KIF18A protein, human
  • Kinesin

Associated data

  • GENBANK/BC048347