The Circadian Clock in Cyanobacteria Ensures Successful DNA Replication

Self-sustaining oscillations on the timescale of a day, known as circadian rhythms, are commonly found in living systems, but the underlying selective pressures that favor a dynamical system with stable oscillations remain unclear. Cyanobacteria have the most ancient circadian clock known and present a powerful model system to investigate questions of mechanism and fitness, and previous work has shown that this clock is coupled intimately to the metabolism of the cell. Using numerical simulations, we argue that a stable oscillator is a biochemically viable solution to the problem of inferring the metabolic state hours in the future based on past metabolic information. One essential process that may require future knowledge is DNA replication where completion of the chromosome occurs hours after the decision to initiate a replication cycle. We show that, consistent with this idea, initiation of replication is suppressed by the clock as nightfall approaches. Using live cell imaging approaches we show that the stability of replication forks in the dark depends strongly on the clock state, suggesting that clock control is also needed to allow open replication forks to complete successfully in the night. Consistent with this prediction, we find that "jet-lagged" cells accumulate incomplete chromosomes in the night. We argue that protection of genome integrity from the threat of fluctuating resource availability may have been an ancient driver leading to the creation of circadian rhythms.