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J Cell Biol. 2019 Aug 5;218(8):2529-2544. doi: 10.1083/jcb.201904169. Epub 2019 Jun 27.

High-resolution imaging reveals how the spindle midzone impacts chromosome movement.

Author information

1
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY.
2
Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY.
3
Department of Cancer Biology, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
4
Department of Pharmacology, University of North Carolina, Chapel Hill, NC.
5
Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, and North Carolina State University, Raleigh, NC.
6
Wadsworth Center, New York State Department of Health, Albany, NY.
7
Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
8
Department of Physics and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA.
9
Laboratory of Chemistry and Cell Biology, The Rockefeller University, New York, NY kapoor@rockefeller.edu.

Abstract

In the spindle midzone, microtubules from opposite half-spindles form bundles between segregating chromosomes. Microtubule bundles can either push or restrict chromosome movement during anaphase in different cellular contexts, but how these activities are achieved remains poorly understood. Here, we use high-resolution live-cell imaging to analyze individual microtubule bundles, growing filaments, and chromosome movement in dividing human cells. Within bundles, filament overlap length marked by the cross-linking protein PRC1 decreases during anaphase as chromosome segregation slows. Filament ends within microtubule bundles appear capped despite dynamic PRC1 turnover and submicrometer proximity to growing microtubules. Chromosome segregation distance and rate are increased in two human cell lines when microtubule bundle assembly is prevented via PRC1 knockdown. Upon expressing a mutant PRC1 with reduced microtubule affinity, bundles assemble but chromosome hypersegregation is still observed. We propose that microtubule overlap length reduction, typically linked to pushing forces generated within filament bundles, is needed to properly restrict spindle elongation and position chromosomes within daughter cells.

PMID:
31248912
PMCID:
PMC6683753
[Available on 2020-02-05]
DOI:
10.1083/jcb.201904169

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