Protein recruitment to DNA break sites is an integral part of the DNA damage response (DDR). Elucidation of the hierarchy and temporal order with which DNA damage sensors as well as repair and signaling factors assemble around chromosome breaks has painted a complex picture of tightly regulated macromolecular interactions that build specialized compartments to facilitate repair and maintenance of genome integrity. While many of the underlying interactions, e.g. between repair factors and damage-induced histone marks, can be explained by lock-and-key or induced fit binding models assuming fixed stoichiometries, structurally less well defined interactions, such as the highly dynamic multivalent interactions implicated in phase separation, also participate in the formation of multi-protein assemblies in response to genotoxic stress. Although much remains to be learned about these types of cooperative and highly dynamic interactions and their functional roles, the rapidly growing interest in material properties of biomolecular condensates and in concepts from polymer chemistry and soft matter physics to understand biological processes at different scales holds great promises. Here, we discuss nuclear condensates in the context of genome integrity maintenance, highlighting the cooperative potential between clustered stoichiometric binding and phase separation. Rather than viewing them as opposing scenarios, their combined effects can balance structural specificity with favorable physicochemical properties relevant for the regulation and function of multilayered nuclear condensates.

DNA 断裂位点的蛋白质募集是 DNA 损伤反应 (DDR) 的一个组成部分。阐明 DNA 损伤传感器以及修复和信号因子在染色体断裂周围组装的层次结构和时间顺序，描绘了一幅复杂的图景，即严格调控的大分子相互作用，这些相互作用构建了专门的隔室，以促进基因组完整性的修复和维护。虽然许多潜在的交互，例如修复因子和损伤诱导的组蛋白标记之间的差异，可以通过假设化学计量固定的锁钥匙或诱导拟合结合模型来解释，结构上不太明确的相互作用，例如涉及相分离的高动态多价相互作用，也参与响应基因毒性应激的多蛋白组装体的形成。尽管关于这些类型的合作和高动态相互作用及其功能作用还有很多有待了解，但人们对生物分子缩合物的材料特性以及聚合物化学和软物质物理学概念的迅速增长的兴趣，以了解不同尺度的生物过程具有很大的希望. 在这里，我们在基因组完整性维护的背景下讨论核凝聚物，突出了成簇化学计量结合和相分离之间的合作潜力。与其将它们视为对立的场景，它们的综合效应可以平衡结构特异性与与多层核凝聚物的调节和功能相关的有利物理化学特性。