Circadian gating of cell divisions revealed in single cyanobacterial cells

Qiong Yang (October 29, 2010)

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Cyclic processes in biology span a wide dynamic range, from the sub-second periods of neural spike trains to annual rhythms in animal and plant reproduction. Even an individual cell exposed to a constant environment may exhibit many parallel periodic activities with different frequencies. It is therefore important to elucidate how multiple clocks coordinate their oscillations. Circadian oscillation and cell cycle are the two most essential rhythmic events present in almost all organisms. In several unicellular organisms and higher vertebrates, it has been shown that the circadian system affects whether cell division is permitted. Here, we integrate theoretical and experimental approaches to investigate how the circadian and cell division subsystems are coupled together in single cells of the cyanobacterium Synechococcus elongatus. We simultaneously tracked cell division events and circadian phases of individual cells. We found that the timing of cell divisions is synchronized to circadian signals rather than uniformly distributed throughout the day as expected from un-coupled clocks. This suggests that the circadian clock acts as a 'gate' for cell divisions. We fit the data to a model to determine the gating function that describes when cell cycle progression slows as a function of circadian and cell cycle phases. We infer that cell cycle progression in cyanobacteria slows during a specific circadian interval but is uniform across cell cycle phases. Our model is applicable to the quantification of the coupling between biological oscillators in other organisms.

Work done in Alexander van Oudenaarden laboratory at MIT and in collaboration with Susan Golden at UCSD.

1. Q. Yang*, B. F. Pando*, G. Dong, S. S. Golden, and A. van Oudenaarden. Circadian gating of the cell cycle revealed in single cyanobacterial cells. Science 327, 1522 (2010).
2. G. Dong, Q. Yang, Q. Wang, Y. Kim, T. L. Wood, K. W. Osteryoung, A. van Oudenaarden, and S. S. Golden. Elevated ATPase activity of KaiC applies a circadian checkpoint on cell division in Synechococcus elongatus. Cell 140, 529 (2010).