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J Cell Biol. 2019 Feb 7. pii: jcb.201807228. doi: 10.1083/jcb.201807228. [Epub ahead of print]

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

Author information

1
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.
2
The Jackson Laboratory, Bar Harbor, ME.
3
Department of Pathology, University of Vermont, Burlington, VT.
4
Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN.
5
The Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI.
6
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI.
7
The Jackson Laboratory, Bar Harbor, ME Laura.Reinholdt@jax.org.
8
Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT jstumpff@uvm.edu.

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.

PMID:
30733233
DOI:
10.1083/jcb.201807228

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