Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling
- University of Colorado, Boulder, United States
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Christopher Edelmaier
Meredith D Betterton
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.
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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Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling
eLife 9:e48787.
https://doi.org/10.7554/eLife.48787
