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Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13752-7. doi: 10.1073/pnas.0807007105. Epub 2008 Sep 9.

An integrated mechanobiochemical feedback mechanism describes chromosome motility from prometaphase to anaphase in mitosis.

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Center for Theoretical Biological Physics, University of California at San Diego, La Jolla, CA 92093, USA.


During mitosis, chromosomes undergo a series of movements while being end-on attached to the kinetochore microtubules (KMTs) from spindle poles. The mechanism underlying such movements and their physiological functions remains elusive. We describe a mechanobiochemical feedback model of chromosome motility. The key ingredient is a feedback mechanism between the local chemical reactions that control the dynamics of KMTs and the mechanical state of the chromosome via tension-sensitive proteins localized at the kinetochores. This model can recapitulate all of the essential and distinct features of chromosome motilities from prometaphase to anaphase in a coherent manner. We further show that this feedback mechanism provides robust and precise means of guiding the chromosome to the cell equator regardless of the initial conditions and uncertainty in velocity. Predictions of our model can be tested experimentally.

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