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Spindle checkpoint regulated by nonequilibrium collective spindle-chromosome interaction; relationship to single DNA molecule force-extension formula

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Leif Matsson

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The spindle checkpoint, which blocks segregation until all sister chromatid pairs have been stably connected to the two spindle poles, is perhaps the biggest mystery of the cell cycle. The main reason seems to be that the spatial correlations imposed by microtubules between stably attached kinetochores and the nonlinear dependence of the system on the increasing number of such kinetochores have been disregarded in earlier spindle checkpoint studies. From these missing parts a non-equilibrium collective spindle–chromosome interaction is obtained here for budding yeast (Saccharomyces cerevisiae) cells. The interaction, which is based on a non-equilibrium statistical mechanics, can sense and count the number of stably attached kinetochores and sense the threshold for segregation. It blocks segregation until all sister chromatids pairs have been bi-oriented and regulates tension such that segregation becomes synchronized, thus explaining how the cell might decide to segregate replicated chromosomes. The model also predicts kinetochore oscillations at a frequency which agrees well with observation. Finally, a relationship between this spindle–chromosome dynamics and the force-extension formula obtained in a single DNA molecule experiment is obtained.


PACS

87.14.G- Nucleic acids

87.15.H- Dynamics of biomolecules

87.17.-d Cell processes

Subjects

Biological physics

Dates

Issue 50 (16 December 2009)

Received 1 July 2009, in final form 17 September 2009

Published 13 November 2009



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