Testing of a New Integrated Model of the Yeast START Transition

Title:

Experimental testing of a new integrated model of the budding yeast START transition

Author(s):

N. R. Adames P. L. Schuck K. C. Chen T. M. Murali J. J. Tyson J. Peccoud

Publication:

Published in: Molecular Biology of the Cell
Volume: 26, Issue: 22, Pages: 3966-3984
Published: 11/05/2015
DOI: 10.1091/mbc.E15-06-0358
Website: http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E15-06-0358

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We propose a new model of the yeast start transition. We tested the accuracy of the model by simulating various mutants not described in the literature.

The cell cycle is composed of bistable molecular switches that govern the transitions between gap phases (G1 and G2) and the phases in which DNA is replicated (S) and partitioned between daughter cells (M). Many molecular details of the budding yeast G1-S transition (START) have been elucidated in recent years, especially with regard to its switch-like behavior due to positive feedback mechanisms. These results led us to reevaluate and expand a previous mathematical model of the yeast cell cycle (Chen et al. 2004. Mol Biol Cell 15:3841). The new model incorporates Whi3 inhibition of Cln3 activity, Whi5 inhibition of SBF and MBF transcription factors, and feedback inhibition of Whi5 by G1-S cyclins. We tested the accuracy of the model by simulating various mutants not described in the literature. We then constructed these novel mutant strains, and compared their observed phenotypes to the model’s simulations. The experimental results reported here led to further changes of the model, which will be fully described in a later publication. Our study demonstrates the advantages of combining model design, simulation and testing in a coordinated effort to better understand a complex biological network.

This publication is the product of our collaboration with T.M. Murali in the Department of Computer Science and John Tyson in the Department of Biological Sciences. This work has been funded by NIH Grant R01GM095955.