Circadian Gating of the Cell Cycle Revealed in Single Cyanobacterial Cells

Abstract

Although major progress has been made in uncovering the machinery underlying individual biological clocks, much less is known about how multiple clocks coordinate their oscillations. We present a general framework that describes coupled cyclic processes in single cells and apply this to the interaction between the circadian and cell-division cycles in the cyanobacterium Synechococcus elongatus. We simultaneously track cell-division events and circadian phases of individual cells and use this information to determine when cell-cycle progression is slowed down as a function of circadian and cell-cycle phases. We infer that cell-cycle progression in cyanobacteria slows down during a specific circadian interval, but is uniform across cell-cycle phase. Our framework is applicable to the quantification of the coupling between any biological oscillators in other organisms.

Circadian Rhythms in Cyanobacteria

“…The circadian oscillator is not influenced by the periodicity of the cell cycle and maintains ϳ24-h periodicity independent of whether cells are dividing very rapidly or not at all (13,25,26). Although cell division is not synchronous among cells in the population or with the circadian cycle, the circadian clock regulates or "gates" the timing of cell division, defining a portion of the 24-h cycle in the early night in which cell division is disallowed (12,13,27). Additionally, the clock regulates the superhelical status and compaction of the chromosome (14,15).…”

Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle

“…Therefore, it is reasonable to expect that functional links as above should lead to 1:1 phase locking of the clock and cell cycle when their uncoupled periods are similar. In lower organisms, evidence of circadian coupling has been published for cyanobacteria (7,8). Likewise, phase locking of the cell cycle of budding yeast using periodic forcing of the G1 cyclin CLN2 has been demonstrated (9).…”

The circadian oscillator in Synechococcus elongatus controls metabolite partitioning during diurnal growth

“…Phototrophic cyanobacteria present a completely different engineering challenge relative to heterotrophic bacteria such as Escherichia coli: their cellular activities respond strongly to the presence and absence of light because their metabolism is centered on photosynthesis (6,7). Diverse cyanobacteria also possess a true circadian clock that synchronizes with external LD cycles and has been demonstrated to drive both gene expression and metabolic rhythms (8)(9)(10). It is important to understand how signals from the external environment and the internal circadian clock are integrated to modulate metabolic processes in environmentally relevant LD cycles to optimize the engineering of these organisms.…”