Modeling the Role of Tension in Yeast Kinetochore Microtubule Dynamics

Thursday, June 19, 2003 - 1:00pm - 2:00pm
Lind 409
David Odde (University of Minnesota, Twin Cities)
To properly segregate replicated chromosomes during mitosis requires the formation of a mitotic spindle, which consists of microtubules that emanate from the spindle poles and connect to chromosome-associated kinetochores. Kinetochores track along microtubule plus ends as the microtubules self-assemble and disassemble via dynamic instability. Due to the stochastic nature of microtubule dynamic instability, the sister kinetochores can transiently move away from each other, each kinetochore tracking along a disassembling microtubule. In this case, tension will develop between the kinetochores in the chromatin that links them together. Prior work suggested that tension influences the switching behavior associated with dynamic instability. We found that a Monte Carlo simulation model for microtubule dynamic instability that includes tension-mediated microtubule switching was consistent with experimental observations of both wild-type and replication-deficient GFP-tagged yeast kinetochores during metaphase. This model also requires that a stable spatial gradient of microtubule catastrophe rate exists, with a higher probability of catastrophe (stochastic switching from self-assembly to disassembly) occurring at the spindle equator than at the poles. Together, these processes can account for the spatial organization of yeast kinetochore microtubules and the results suggest that tension in the kinetochore-DNA complex promotes the stabilization of microtubules and protects them from disassembly.

Relevant reference: Brian L. Sprague , Chad G. Pearson , Paul S. Maddox , Kerry S. Bloom , E. D. Salmon and David. J. Odde , Mechanisms of Microtubule-Based Kinetochore Positioning in the Yeast Metaphase Spindle Biophysical Journal 84:3529-3546 (2003)