On the cell cycle and its switches

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Abstract
For the cell-division cycle to progress, hundreds of genes and proteins must be coordinately regulated. Systems-level studies of this cycle show that positive-feedback loops help to keep events in sync. The cell cycle couples growth and cell division to ensure the consistent size and shape of individual cells. This involves a vast array of genes and proteins, and requires sophisticated mechanisms to keep them acting in step. Two reports in this issue focus on different points in the cell cycle of the budding yeast Saccharomyces cerevisiae, and find that in each case, positive feedback keeps the process on the rails. Skotheim et al. studied the Start checkpoint in the G1 cell cycle phase, where cells irreversibly commit to cell division. Single-cell analysis reveals that Start is a positive feedback-dependent switch that coordinates the simultaneous transcription of a large group of cell cycle genes and the budding of a daughter cell. Holt et al. studied the onset of anaphase in mitosis, at which chromosome pairs separate abruptly and simultaneously. Cohesion between sister chromatids is dissolved by the enzyme separase, which is held in check by securin. A positive feedback loop regulating the ubiquitination and destruction of securin appears to make anaphase a switch-like event.