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Using default constraints of the spindle assembly checkpoint to estimate the associated chemical rates

BACKGROUND: 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 fe...

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Detalles Bibliográficos
Autores principales: Dao Duc, Khanh, Holcman, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368725/
https://www.ncbi.nlm.nih.gov/pubmed/22260411
http://dx.doi.org/10.1186/2046-1682-5-1
Descripción
Sumario:BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.