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Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling

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Cite this article as: eLife 2020;9:e48787 doi: 10.7554/eLife.48787

Abstract

The essential functions required for mitotic spindle assembly and chromosome biorientation and segregation are not fully understood, despite extensive study. To illuminate the combinations of ingredients most important to align and segregate chromosomes and simultaneously assemble a bipolar spindle, we developed a computational model of fission-yeast mitosis. Robust chromosome biorientation requires progressive restriction of attachment geometry, destabilization of misaligned attachments, and attachment force dependence. Large spindle length fluctuations can occur when the kinetochore-microtubule attachment lifetime is long. The primary spindle force generators are kinesin-5 motors and crosslinkers in early mitosis, while interkinetochore stretch becomes important after biorientation. The same mechanisms that contribute to persistent biorientation lead to segregation of chromosomes to the poles after anaphase onset. This model therefore provides a framework to interrogate key requirements for robust chromosome biorientation, spindle length regulation, and force generation in the spindle.

Article and author information

Author details

  1. Christopher Edelmaier

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3673-1310
  2. Adam R Lamson

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zachary R Gergely

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Saad Ansari

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Blackwell

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. J Richard McIntosh

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthew A Glaser

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Meredith D Betterton

    Department of Physics, University of Colorado, Boulder, Boulder, United States
    For correspondence
    mdb@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5430-5518

Funding

National Science Foundation (DMR1725065)

  • Meredith D Betterton

National Science Foundation (DMS1620003)

  • Matthew A Glaser
  • Meredith D Betterton

National Science Foundation (DMR1420736)

  • Matthew A Glaser

National Institutes of Health (K25GM110486)

  • Meredith D Betterton

National Institutes of Health (R01GM124371)

  • Meredith D Betterton

NIH/University of Colorado Biophysics Training Program (Fellowship)

  • Adam R Lamson

National Science Foundation (ACI1532235)

  • Christopher Edelmaier
  • Adam R Lamson
  • Zachary R Gergely
  • Saad Ansari
  • Robert Blackwell
  • J Richard McIntosh
  • Matthew A Glaser
  • Meredith D Betterton

National Science Foundation (ACI153223)

  • Christopher Edelmaier
  • Adam R Lamson
  • Zachary R Gergely
  • Saad Ansari
  • Robert Blackwell
  • J Richard McIntosh
  • Matthew A Glaser
  • Meredith D Betterton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jennifer G. DeLuca, Colorado State University, United States

Publication history

  1. Received: May 24, 2019
  2. Accepted: February 12, 2020
  3. Accepted Manuscript published: February 13, 2020 (version 1)

Copyright

© 2020, Edelmaier et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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