Discrete gene replication events drive coupling between the cell cycle and circadian clocks

Area of Science:

• Cellular Biology
• Systems Biology
• Biophysics

Background:

• Organisms utilize a cell cycle for DNA replication and a circadian clock for daily rhythm anticipation.
• Known cross-regulatory interactions exist between cell cycle and circadian clock systems.
• The cell cycle's impact on circadian clocks is often considered specific, not generic.

Purpose of the Study:

• To investigate the generic, nonspecific influence of the cell cycle on circadian clock function using mathematical modeling.
• To identify mechanisms that protect circadian clocks from cell cycle-driven disturbances.
• To explain the robustness of the circadian clock in Synechococcus elongatus.

Main Methods:

• Mathematical modeling of coupled cell cycle and circadian clock systems.
• Analysis of negative transcriptional feedback loops in circadian clocks.
• Investigation of protective mechanisms in Synechococcus elongatus, including phosphorylation-based oscillators and multi-copy chromosome replication.

Main Results:

• Cell cycle DNA replication generically drives circadian clocks, potentially impairing their function.
• Circadian clocks with negative transcriptional feedback can phase-lock to the cell cycle or exhibit erratic behavior.
• Synechococcus elongatus employs a phosphorylation-based oscillator and multiple chromosome copies to insulate its clock from cell cycle perturbations.

Conclusions:

• The cell cycle exerts a generic, disruptive influence on circadian clocks through DNA replication.
• Robustness in Synechococcus elongatus's circadian clock is achieved through a combination of a modified oscillator and genetic redundancy.
• Understanding these interactions is crucial for comprehending biological timing mechanisms in diverse organisms.