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


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
01 04 2019
Historique:
received: 31 07 2018
revised: 21 11 2018
accepted: 09 01 2019
pubmed: 9 2 2019
medline: 14 4 2020
entrez: 9 2 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 30733233
pii: jcb.201807228
doi: 10.1083/jcb.201807228
pmc: PMC6446859
doi:

Substances chimiques

KIF18a protein, mouse 0
TP53 protein, human 0
Tumor Suppressor Protein p53 0
KIF18A protein, human EC 3.6.1.-
Kinesins EC 3.6.4.4

Banques de données

GENBANK
['BC048347']

Types de publication

Journal Article 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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1148-1163

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM086610
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121491
Pays : United States
Organisme : NICHD NIH HHS
ID : R03 HD078485
Pays : United States
Organisme : NIH HHS
ID : S10 OD018175
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2019 Fonseca et al.

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Auteurs

Cindy L Fonseca (CL)

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.

Heidi L H Malaby (HLH)

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.

Leslie A Sepaniac (LA)

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.

Whitney Martin (W)

The Jackson Laboratory, Bar Harbor, ME.

Candice Byers (C)

The Jackson Laboratory, Bar Harbor, ME.

Anne Czechanski (A)

The Jackson Laboratory, Bar Harbor, ME.

Dana Messinger (D)

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT.

Mary Tang (M)

Department of Pathology, University of Vermont, Burlington, VT.

Ryoma Ohi (R)

Department of Cell and Developmental Biology, Vanderbilt University Medical School, Nashville, TN.
The Life Sciences Institute, University of Michigan Medical School, Ann Arbor, MI.
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI.

Laura G Reinholdt (LG)

The Jackson Laboratory, Bar Harbor, ME Laura.Reinholdt@jax.org.

Jason Stumpff (J)

Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT jstumpff@uvm.edu.

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