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Driving the cell cycle with a minimal CDK control network

Abstract

Control of eukaryotic cell proliferation involves an extended regulatory network, the complexity of which has made it difficult to understand the basic principles of the cell cycle. To investigate the core engine of the mitotic cycle we have generated a minimal control network in fission yeast that efficiently sustains cellular reproduction. Here we demonstrate that orderly progression through the major events of the cell cycle can be driven by oscillation of an engineered monomolecular cyclin-dependent protein kinase (CDK) module lacking much of the canonical regulation. We show further that the CDK oscillator acts as the primary organizer of the cell cycle, imposing timing and directionality to a system of two CDK activity thresholds that define independent cell cycle phases. We propose that this simple core architecture forms the basic control of the eukaryotic cell cycle.

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Figure 1: A Cdc13-L-Cdc2 fusion in fission yeast.
Figure 2: Oscillation of a single CDK activity between two thresholds.
Figure 3: Resetting the cell cycle.
Figure 4: Timing and directionality of the minimal cell cycle.
Figure 5: Role of Cdc2 T14 and Y15 phosphorylation.

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Acknowledgements

We thank J. Hayles, P.-Y. Wu and F. Navarro for critically reading the manuscript, and N. Rhind for the anti-Cds1 antibody. D.C. was supported by post-doctoral fellowships from EMBO (ALTF 899-2007) and the Human Frontier Science Program (LT00623/2008) and P.N. by the Breast Cancer Research Foundation, The Rockefeller University and the Anderson Cancer Center Research at Rockefeller University.

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D.C. designed and performed the experiments and wrote the manuscript. Both authors discussed the experiments and edited the manuscript.

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Correspondence to Damien Coudreuse.

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The file contains Supplementary Figures 1-20 with legends and Supplementary Table 1. A corrected file was uploaded on 23 February 2011 as it was noticed that figures 5 and 6 had been transposed in the original version. (PDF 3246 kb)

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Coudreuse, D., Nurse, P. Driving the cell cycle with a minimal CDK control network. Nature 468, 1074–1079 (2010). https://doi.org/10.1038/nature09543

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