Four-dimensional control of the cell cycle

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 repl ication is completed and any damaged DNA is repaired, and that DNA replicat ion normally follows mitosis. This is achieved by the synthesis and destruc tion 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, lar gely 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 h ow the locations of the main components of the cell-cycle machinery are reg ulated as part of the mechanism by which the cell controls when and how it replicates and divides.