The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations, and multi-contact 3C and find that, by contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interphase state during mitotic exit. Most mitotic entanglements are removed during anaphase/telophase, with remaining ones removed during early G1, in a topoisomerase-II-dependent process. Polymer models suggest a two-stage disentanglement pathway: first, decondensation of mitotic chromosomes with remaining condensin loops produces entropic forces that bias topoisomerase II activity toward decatenation. At the second stage, the loops are released, and the formation of new entanglements is prevented by lower topoisomerase II activity, allowing the establishment of unentangled and territorial G1 chromosomes. When mitotic entanglements are not removed in experiments and models, a normal interphase state cannot be acquired.

染色体的拓扑状态决定了它们的机械特性、动力学和功能。最近的研究表明，间期染色体基本上没有缠结。在这里，我们使用 Hi-C、聚合物模拟和多接触 3C，发现相比之下，有丝分裂染色体是自缠结的。我们探索有丝分裂自缠结状态如何在有丝分裂退出期间转化为非缠结间期状态。大多数有丝分裂缠结在后期/末期被去除，其余的则在 G1 早期被去除，这是一个依赖于拓扑异构酶 II 的过程。聚合物模型提出了一个两阶段的解缠结途径：首先，有丝分裂染色体与剩余凝缩环的去浓缩产生熵力，使拓扑异构酶 II 活性偏向去连接。在第二阶段，环被释放，并且通过降低拓扑异构酶 II 活性来阻止新缠结的形成，从而允许建立未缠结的区域性 G1 染色体。当实验和模型中没有去除有丝分裂缠结时，就无法获得正常的间期状态。