Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryotic cell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specific timing and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced cell division. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that a minimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) and Clb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionary conservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional (“healthy”) phenotypes require the capacity to oscillate autonomously whereas dysfunctional (potentially “diseased”) phenotypes may lack this capacity.

一些生物网络在其成分中表现出振荡，以将刺激转换为时间依赖性反应。真核细胞周期就是这种情况，受周期蛋白依赖性激酶（cyclin / Cdk）活动的波动控制，这些活动在特定的时间上升和下降并保证其及时发生。细胞周期蛋白/ Cdk振荡的中断可能通过减少细胞分裂而导致功能障碍。因此，捕获表现出稳健振荡的网络设计的特性是令人感兴趣的。在这里，我们显示了最小的酵母细胞周期网络能够自主振荡，并且在已知的和假设的网络设计中，细胞周期蛋白/ Cdk介导的正反馈回路（PFL）和以Clb3为中心的调节维持细胞周期蛋白/ Cdk的振荡。我们建议，Clb3介导的细胞周期蛋白/ Cdk波的协调调和检查点和振荡细胞周期模型。考虑到跨真核细胞的cyclin / Cdk网络的进化保守性，我们假设功能性（“健康”）表型需要具有自主振荡的能力，而功能失调（可能是“病态”）表型可能缺乏这种能力。