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Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle

Nature volume 401, pages 394–397 (1999)Cite this article

Abstract

In yeast and somatic cells, mechanisms ensure cell-cycle events are initiated only when preceding events have been completed1. In contrast, interruption of specific cell-cycle processes in early embryonic cells of many organisms does not affect the timing of subsequent events2, indicating that cell-cycle events are triggered by a free-running cell-cycle oscillator. Here we present evidence for an independent cell-cycle oscillator in the budding yeast Saccharomyces cerevisiae. We observed periodic activation of events normally restricted to the G1 phase of the cell cycle, in cells lacking mitotic cyclin-dependent kinase activities that are essential for cell-cycle progression. As in embryonic cells, G1 events cycled on schedule, in the absence of S phase or mitosis, with a period similar to the cell-cycle time of wild-type cells. Oscillations of similar periodicity were observed in cells responding to mating pheromone in the absence of G1 cyclin (Cln)- and mitotic cyclin (Clb)-associated kinase activity, indicating that the oscillator may function independently of cyclin-dependent kinase dynamics. We also show that Clb-associated kinase activity is essential for ensuring dependencies by preventing the initiation of new G1 events when cell-cycle progression is delayed.

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Figure 1: G1-specific transcription, budding cycles and Cln2-associated kinase activity in wild-type cells and cells lacking Clb activity.
Figure 2: Synchronous mating projection cycles in a cln1,2,3-null mutant cells have similar kinetics to budding cycles in clb1,2,3,4,5,6 mutant cells.
Figure 3: Clb activity is required to prevent the activation of G1 transcription.

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Acknowledgements

We thank R. Deshaies for the stabilized Sic1-Δ3P construct; D. Stuart for the triple cln null mutant strain; M. Grunstein for the HTA1/PRT1 probe; C. Wittenberg, N. Rhind and K. Sato for critical review of the manuscript; and members of the Reed laboratory for helpful discussions. This work was supported in part by the Leukemia Society of America and the NIH.

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  1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 94303, California, USA

    Steven B. Haase & Steven I. Reed

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Correspondence to Steven I. Reed.

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Haase, S., Reed, S. Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle. Nature 401, 394–397 (1999). https://doi.org/10.1038/43927

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