In silico study of kinetochore control, amplification, and inhibition effects in MCC assembly

Bio Systems
Bashar IbrahimStephan Diekmann

Abstract

Eukaryotic cells rely on a surveillance mechanism, the "Spindle Assembly Checkpoint"SACM in order to ensure accurate chromosome segregation by preventing anaphase initiation until all chromosomes are correctly attached to the mitotic spindle. In different organisms, a mitotic checkpoint complex (MCC) composed of Mad2, Bub3, BubR1/Mad3, and Cdc20 inhibits the anaphase promoting complex (APC/C) to initiate promotion into anaphase. The mechanism of MCC formation and its regulation by the kinetochore are unclear. Here, we constructed dynamical models of MCC formation involving different kinetochore control mechanisms including amplification as well as inhibition effects, and analysed their quantitative properties. In particular, in this system, fast and stable metaphase to anaphase transition can only be triggered when the kinetochore controls the Bub3:BubR1-related reactions; signal amplification and inhibition play a subordinate role. Furthermore, when introducing experimentally determined parameter values into the models analysed here, we found that effective MCC formation is not combined with complete Cdc20 sequestering. Instead, the MCC might bind and completely block the APC/C. The SACM might function by an MCC:APC/C complex ...Continue Reading

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Apr 9, 2013·Progress in Biophysics and Molecular Biology·Sergej TschernyschkowBashar Ibrahim
Oct 17, 2012·PloS One·Peter KreyssigPeter Dittrich
Oct 23, 2014·International Journal of Molecular Sciences·Bashar Ibrahim, Richard Henze
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Nov 23, 2017·Mathematical Biosciences and Engineering : MBE·Bashar Ibrahim
Jan 1, 2016·AIMS Molecular Science·Song-Tao Liu, Hang Zhang

Related Concepts

Meiotic Spindle Apparatus
Kinetochores
Chromosomes
Gene Rearrangement
Mitosis
APC gene
MAX Interacting Protein 1
Anaphase-promoting complex
Chromosome Segregation
DNA Amplification

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