Mitosis ensures the proper segregation of chromosomes into daughter cells, which is accomplished by the mitotic spindle. During fission yeast mitosis, chromosomes establish bi-orientation as the bipolar spindle assembles, meaning that sister kinetochores become attached to microtubules whose growth was initiated by the two sister poles. This process includes mechanisms that correct erroneous attachments made by the kinetochores during the attachment process. This thesis presents a 3D physical model of spindle assembly in a Brownian dynamics-kinetic Monte Carlo simulation framework and a realistic description of the physics of microtubule, kinetochore, and chromosome dynamics, in order to interrogate the dynamics and mechanisms of chromosome bi-orientation and error correction. We have added chromosomes to our previous physical model of spindle assembly, which included microtubules, a spherical nuclear envelope, motor proteins, crosslinking proteins, and spindle pole bodies (centrosomes). In this work, we have explored the mechanical properties of kinetochores and their interactions with microtubules that achieve amphitelic spindle attachments at high frequency. A minimal physical model yields simulations that generate chromosome attachment errors, but resolves them, much as normal chromosomes do.
|Advisor:||Betterton, Meredith D., Glaser, Matthew A.|
|Commitee:||Hough, Loren, McIntosh, Richard, Perkins, Thomas|
|School:||University of Colorado at Boulder|
|School Location:||United States -- Colorado|
|Source:||DAI-B 80/02(E), Dissertation Abstracts International|
|Subjects:||Statistical physics, Cellular biology, Biophysics|
|Keywords:||Computational, Fission, Mitosis, Nonequilibrium, Yeast|
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