Abstract：
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.
摘要：
染色体的拓扑状态决定了它们的机械性质,动力学,和功能。最近的工作表明，间期染色体基本上没有缠结。这里,我们用Hi-C,聚合物模拟，和多触点3C，发现，相比之下,有丝分裂染色体是自我纠缠的。我们探索有丝分裂自缠结状态在有丝分裂退出过程中如何转化为未缠结的相间状态。大多数有丝分裂缠结在后期/末期被去除，在拓扑异构酶II依赖性过程中，其余的在G1早期被去除。聚合物模型提出了一个两阶段的解开途径：首先，有丝分裂染色体与剩余的凝缩蛋白环的解凝聚会产生熵力，使拓扑异构酶II的活性偏向于decatenation。在第二阶段,循环被释放，较低的拓扑异构酶II活性阻止了新缠结的形成，允许建立未缠结和领土G1染色体。当有丝分裂缠结在实验和模型中没有被去除时，无法获得正常的相间状态。
