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Amplitude control of cell-cycle waves by nuclear import

Nature Cell Biology volume 6, pages 451–457 (2004)Cite this article

Abstract

Propagation of waves of biochemical activities through consecutive stages of the cell cycle is essential to execute the steps of cell division in a strict temporal order. Mechanisms that ensure the proper amplitude and timing of these waves are poorly understood1. Using a synthetic gene circuit, we show that a transcriptional activator driven by yeast cell-cycle promoters propagates transcriptional oscillations with substantial damping. Although regulated nuclear translocation has been implicated in the timing of oscillatory events2,3, mathematical analysis shows that increasing the rate of nuclear transport is an example of a general regulatory principle, which enhances the fidelity of wave propagation. Indeed, increasing the constitutive import rate of the activator counteracts the damping of waves and concurrently preserves the intensity of the signal. In contrast to the regulatory range of nuclear transport, the range of mRNA turnover considerably limits transcriptional wave propagation. This classification of cellular processes outlines potential regulatory mechanisms that can contribute to faithful transmission of oscillations at different stages of the cell cycle.

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Figure 1: Constructs and properties of the transmission process.
Figure 2: Mathematical analysis of propagation of transcriptional oscillations.
Figure 3: Import rates of rtTA constructs and their effect on the PTR of the transmitted waves.
Figure 4: Transcript levels of untagged and NLS-tagged PCLN2-rtTA, and PTETO2CYC1-lacZ genes.
Figure 5: Attenuation of oscillations during the transmission process.

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Acknowledgements

We are indebted to A. Amon at the Center for Cancer Research, Massachusetts Institute of Technology, for discussions throughout the progress of this work and for her support to M.G.B. We thank H. Blitzblau, I. W. Mattaj and A. Varshavsky for discussions, and W. Hillen for the rtTA(S2) construct. A.B. is a Long Term Fellow of the Human Frontiers Science Program. This work was supported by a grant from the National Institutes of Health (grant GM068957).

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Authors and Affiliations

  1. Department of Physics, Massachusetts Institute of Technology, 13-2008, Cambridge, 02139, MA, USA

    Attila Becskei & Alexander van Oudenaarden

  2. Center for Cancer Research, Massachusetts Institute of Technology, E17-233, Cambridge, 02139, MA, USA

    Monica G. Boselli

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Correspondence to Alexander van Oudenaarden.

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Becskei, A., Boselli, M. & Oudenaarden, A. Amplitude control of cell-cycle waves by nuclear import. Nat Cell Biol 6, 451–457 (2004). https://doi.org/10.1038/ncb1124

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