Mechanisms of chromosome biorientation and bipolar spindle assembly analyzed by computational modeling Journal Article uri icon



  • AbstractThe 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.

publication date

  • May 24, 2019

has restriction

  • green

Date in CU Experts

  • December 27, 2020 11:17 AM

Full Author List

  • Edelmaier CJ; Lamson AR; Gergely ZR; Ansari S; Blackwell R; McIntosh JR; Glaser MA; Betterton MD

author count

  • 8

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