Using default constraints of the spindle assembly checkpoint to estimate the associated chemical rates
Institute for Biology (IBENS), Group of Computational Biology and Applied Mathematics, Ecole Normale Supérieure, 46 rue d'Ulm 75005 Paris, France
BMC Biophysics 2012, 5:1 doi:10.1186/2046-1682-5-1Published: 19 January 2012
Default activation of the spindle assembly checkpoint provides severe constraints on the underlying biochemical activation rates: on one hand, the cell cannot divide before all chromosomes are aligned, but on the other hand, when they are ready, the separation is quite fast, lasting a few minutes. Our purpose is to use these opposed constraints to estimate the associated chemical rates.
To analyze the above constraints, we develop a markovian model to describe the dynamics of Cdc20 molecules. We compute the probability for no APC/C activation before time t, the distribution of Cdc20 at equilibrium and the mean time to complete APC/C activation after all chromosomes are attached.
By studying Cdc20 inhibition and the activation time, we obtain a range for the main chemical reaction rates regulating the spindle assembly checkpoint and transition to anaphase.