Cell cycle oscillations driven by two interlinked bistable switches

Abstract

Regular transitions between interphase and mitosis during the cell cycle are driven by changes in the activity of the enzymatic protein complex cyclin B with cyclin-dependent kinase 1 (Cdk1). At the most basic level, this cell cycle oscillator is driven by negative feedback: active cyclin B Cdk1 activates the Anaphase-Promoting Complex - Cyclosome, which triggers the degradation of cyclin B. Such cell cycle oscillations occur fast and periodically in the early embryos of the frog Xenopus laevis, where several positive feedback loops leading to bistable switches in parts of the regulatory network have been experimentally identified. Here, we build cell cycle oscillator models to show how single and multiple bistable switches in parts of the underlying regulatory network change the properties of the oscillations and how they can confer robustness to the oscillator. We present a detailed bifurcation analysis of these models.