Cell cycle transitions result from global changes in protein phosphorylation states triggered by cyclin-dependent kinases (CDKs). To understand how this complexity produces an ordered and rapid cellular reorganisation, we generated a high-resolution map of changing phosphosites throughout unperturbed early cell cycles in single Xenopus embryos, derived the emergent principles through systems biology analysis, and tested them by biophysical modelling and biochemical experiments. We found that most dynamic phosphosites share two key characteristics: they occur on highly disordered proteins that localise to membraneless organelles, and are CDK targets. Furthermore, CDK-mediated multisite phosphorylation can switch homotypic interactions of such proteins between favourable and inhibitory modes for biomolecular condensate formation. These results provide insight into the molecular mechanisms and kinetics of mitotic cellular reorganisation.

细胞周期转变是由细胞周期蛋白依赖性激酶 (CDK) 触发的蛋白质磷酸化状态的整体变化引起的。为了了解这种复杂性如何产生有序且快速的细胞重组，我们生成了单个非洲爪蟾胚胎中未受干扰的早期细胞周期中磷酸位点变化的高分辨率图，通过系统生物学分析得出了涌现原理，并通过生物物理模型和生物化学对其进行了测试实验。我们发现大多数动态磷酸位点都有两个关键特征：它们出现在定位于无膜细胞器的高度无序的蛋白质上，并且是 CDK 的靶标。此外，CDK介导的多位点磷酸化可以在生物分子凝聚体形成的有利模式和抑制模式之间切换此类蛋白质的同型相互作用。这些结果提供了对有丝分裂细胞重组的分子机制和动力学的深入了解。