Mitotic chromosome alignment ensures mitotic fidelity by promoting interchromosomal compaction during anaphase
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 07, 2019
- Source ID
- 10.1083/jcb.201807228
Entities
People
- Anne Czechanski
- Candice Byers
- Cindy L. Fonseca
- Dana Messinger
- Heidi L H Malaby
- Jason Stumpff
- Laura G Reinholdt
- Leslie A. Sepaniac
- Mary Tang
- Ryoma Ohi
- Whitney Martin
Organizations
- Jackson Laboratory
- National Institutes of Health
- Susan G. Komen for the Cure
- United States Department of Defense
- University of Michigan
- University of Vermont
- Vanderbilt University
- Vermont Space Grant Consortium