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Yeast Cells Can Enter a Quiescent State through G₁, S, G₂, or M Phase of the Cell Cycle¹

Department of Biochemistry and Molecular Biology, Kenneth Norris Jr. Cancer Hospital and Research Institute, University of Southern California School of Medicine, Los Angeles, California 90033 [W. W., D. B.]; and Imperial Cancer Research Fund Cell Cycle Group, Microbiology Unit, University of Oxford, Oxford OX1 3QU, United Kingdom [P. N.]

We have examined the ability of the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae to enter a quiescent state through G₁, S, G₂, or M phase of the cell cycle. We monitored entry to a quiescent state by measuring two well known properties of quiescent cells, i.e., long-term viability and a dramatic increase in resistance to thermal heat shock relative to cycling cells. For this purpose, we made use of yeast cell division cycle (cdc) mutants with which we could arrest most of the cells in culture at specific points in the cell cycle. We find that these eukaryotes can enter a reversible quiescent state at any of the points in the cell cycle we examined if the cells are exposed to starvation conditions (starvation normally signals cells to leave the cell cycle). These findings indicate that mechanisms involved in entry to and exit from a quiescent state can operate not only in G₁ phase (leading to G₀ arrested cells) but can also operate in S, G₂, and M phases of the cell cycle. These findings may be important for clinical oncology in cases where tumor cells escape the cytotoxic effects of chemotherapeutic agents. It may be that escape from the effect of these drugs is due to tumor cells entering quiescent states at points in the cell cycle other than G₁ phase. Perhaps different chemotherapeutic strategies may be required to kill tumor cells reentering the cell cycle from other than G₁.

¹ This work was supported by the Imperial Cancer Research Fund, Medical Research Council (P. N.) and National Cancer Institute Grant CA 50261 and by Grant 2RT0437 from the University of California Tobacco-Related Disease Research Program (D. B.).

² To whom requests for reprints should be addressed, at Norris Cancer Center, 1441 Eastlake Avenue, Los Angeles, CA 90033.

Received 12/14/92. Accepted 2/11/93.

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