A Theoretical Model for the Cell Cycle and Drug Induced Cell Cycle Arrest of FUCCI Systems with Cell-to-Cell Variation during Mitosis

Pharmaceutical Research
Hyeonjeong BaeHyuk-Jin Cha

Abstract

Since the molecular mechanism of the cell cycle was established, various theoretical models of this process have been developed. A recent study revealed significant variability in cell cycle duration between mother and daughter cells, but this observation has not been incorporated into the theoretical models. We used fluorescent ubiquitination-based cell cycle indicator (FUCCI) systems and live-monitored the heterogeneity of cell cycle progression within daughter cells, which accounts for dephasing synchrony. To incorporate the variable cell cycle durations into a model, we modified a two-ordinary differential equation (ODE) model based on reciprocal activation between CDK1 and APC. Our model reproduced the experimental population profile, in which cell cycle synchrony dephased due to variability. Based on this model, we determined parameters for CDK1 and APC in the cell cycle profile after treatment with antimitotic drugs and associated the parameters with the drugs' mode of action as cell cycle inhibitors. This suggests that this model is useful for determining the mode of action of unknown small molecules on the cell cycle.

References

Nov 1, 1968·Biophysical Journal·B V BronkA Paskin
Aug 1, 1997·Computer Applications in the Biosciences : CABIOS·J H Hofmeyr, A Cornish-Bowden
Nov 15, 2002·Nature·Albert Goldbeter
Dec 1, 1964·Experimental Cell Research·J ENGELBERG
Nov 1, 1964·Experimental Cell Research·E C ANDERSON, D F PETERSON
Mar 3, 2004·The Journal of Biological Chemistry·Nozomi SugimotoMasatoshi Fujita
May 7, 2004·Journal of Cell Science·Stéphanie DutertreBernard Ducommun
Sep 24, 2004·Current Biology : CB·Hartmut C Vodermaier
Apr 7, 2007·Proceedings of the National Academy of Sciences of the United States of America·Simone PigolottiMogens H Jensen
Feb 13, 2008·Cell·Asako Sakaue-SawanoAtsushi Miyawaki
Feb 28, 2008·PloS One·Maria I Davidich, Stefan Bornholdt
Mar 28, 2008·Nature Cell Biology·Guang YaoLingchong You
Dec 4, 2008·Fundamental & Clinical Pharmacology·Sylvain GoutellePascal Maire
Feb 4, 2010·PloS One·Karan ManglaMark A Horowitz
Apr 24, 2010·Developmental Cell·Olivier Gavet, Jonathon Pines
Mar 19, 2011·Cell·James E FerrellQiong Yang
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mark R DowlingPhilip D Hodgkin
Nov 21, 2014·The Journal of Biological Chemistry·Lindsay F RizzardiJeanette Gowen Cook
Jan 31, 2015·Nature Reviews. Drug Discovery·Uzma AsgharErik S Knudsen
Mar 5, 2015·Journal of Cellular Biochemistry·Jin-Ju KimHyuk-Jin Cha
Nov 23, 2015·Molecular Cell·Carmen Dominguez-BrauerTak W Mak
Dec 17, 2015·Development, Growth & Differentiation·Takashi Saitou, Takeshi Imamura
Mar 28, 2016·Cancer Treatment Reviews·Erika Hamilton, Jeffrey R Infante

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Citations

Aug 23, 2019·Journal of the Royal Society, Interface·Sean T VittadelloMatthew J Simpson

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Methods Mentioned

BETA
biosensor
FRET

Software Mentioned

harmony
STAT
Photoscape
JULI
FORTRAN
Stage
GraphPad Prism
Operetta

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