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Four-dimensional control of the cell cycle

Abstract

The cell-division cycle has to be regulated in both time and space. In the time dimension, the cell ensures that mitosis does not begin until DNA replication is completed and any damaged DNA is repaired, and that DNA replication normally follows mitosis. This is achieved by the synthesis and destruction of specific cell-cycle regulators at the right time in the cell cycle. In the spatial dimension, the cell coordinates dramatic reorganizations of the subcellular architecture at the entrance to and exit from mitosis, largely through the actions of protein kinases and phosphatases that are often localized to specific subcellular structures. Evidence is now accumulating to suggest that the spatial organization of cell-cycle regulators is also important in the temporal control of the cell cycle. Here I will focus on how the locations of the main components of the cell-cycle machinery are regulated as part of the mechanism by which the cell controls when and how it replicates and divides.

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Figure 1: Temporal control of the animal cell cycle.
Figure 2: Spatial control of the cell cycle.
Figure 3: The nuclear and cytoplasmic roles of Far1.
Figure 4: Nuclear export of CDC25 prevents mitosis when DNA is damaged in fission yeast.
Figure 5: The spindle-assembly checkpoint.

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Acknowledgements

My apologies to all those colleagues whose work had to be referenced indirectly, through the citation of other reviews, because of space limitations. I thank M. Blondel and M. Peter for communicating unpublished results on Far1; D. Lew for putting me right on the morphogenesis checkpoint; M. Zernicka-Goetz for comments on the manuscript; and the CRC, the AICR and the MRC for financial support.

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Pines, J. Four-dimensional control of the cell cycle. Nat Cell Biol 1, E73–E79 (1999). https://doi.org/10.1038/11041

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