Feedback loops and reciprocal regulation: recurring motifs in the systems biology of the cell cycle

• Recurring motifs are found in eukaryotic cell cycle regulation.
• These include positive and negative feedbacks and reciprocal regulation.
• We review examples of all of these and discuss what functions they perform.

The study of eukaryotic cell cycle regulation over the last several decades has led to a remarkably detailed understanding of the complex regulatory system that drives this fundamental process. This allows us to now look for recurring motifs in the regulatory system. Among these are negative feedback loops, which underpin checkpoints and generate cell cycle oscillations; positive feedback loops, which promote oscillations and make cell cycle transitions switch-like and unidirectional; and reciprocal regulation, which can increase the control a key regulator exerts. These simple motifs are found at multiple points in the cell cycle (e.g. S-phase and M-phase control) and are conserved in diverse organisms. These findings argue for an underlying unity in the principles of cell cycle control.