发表机构
Indian Institute of Science Education and Research (IISER-Pune)（印度科学教育研究所（浦那））
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究通过珠-弹簧模型揭示ParABS系统诱导的拓扑修饰产生熵排斥，驱动C. crescentus染色体分离并定量重现实验观测的oriC轨迹与Hi-C特征。
AI 中文摘要
我们识别出一种熵介导的机制，该机制 underlie 细菌细胞 Caulobacter crescentus 中染色体的时空组织。复制中的 DNA 片段之间的有效熵相互作用源于由瞬态 ParA-ParB 结合引起的子代 DNA 聚合物的拓扑修饰。由 ParABS 系统产生的焓贡献进一步影响其动力学。在 C. crescentus 中，染色体复制和分离在细胞分裂前同时发生。C. crescentus 母体染色体的复制起点 oriC 被拴系在旧细胞极。复制产生两个子代 oriC，其中一个保持锚定在旧极。另一个 oriC 由 ParABS 蛋白系统主动运输向新极，即使链的其余部分复制仍在进行中。ParABS 如何在染色体复制期间产生定向力以将子代 oriC 运输到相反极仍不清楚。此外，两个子代染色体被整齐地分离到细胞的两半中。在复制中的 C. crescentus 染色体的珠-弹簧聚合物模型中，我们模拟瞬态 ParA-ParB 接触，这些接触产生 DNA 环和有效的熵排斥。这种排斥驱动染色体分离，并产生与实验一致的 oriC 轨迹，得益于新极附近的 ParA 浓度梯度。这个最小框架，结合拓扑修饰（ToMo）聚合物的物理，使我们能够定量重现多个实验中观察到的不同标记位点和复制体的时间依赖性空间组织。结合一个最小的挤出模型，我们还能恢复染色体臂的线性排列，正如从 Hi-C 图谱的特征对角线所推断的那样。
英文摘要
We identify an entropy-mediated mechanism underlying the spatiotemporal organization of the chromosome in the bacterial cell Caulobacter crescentus. Effective entropic interactions between replicating DNA segments emerge from their topological modifications of daughter DNA polymers caused by transient ParA-ParB binding. Enthalpic contributions arising from the ParABS system further influence their dynamics. In C. crescentus, chromosome replication and segregation occur concurrently before cell division. The origin of replication oriC of the mother chromosome of C. crescentus is tethered to the old cell pole. Replication generates two daughter oriCs, one of which remains anchored at the old pole. The other oriC is actively transported toward the new pole by the ParABS system of proteins even as replication of the rest of the chain is in progress. How ParABS generates a directed force to transport a daughter oriC to the opposite pole during chromosome replication remains unclear. Furthermore, the two daughter chromosomes get neatly segregated into two halves of the cell. In a bead-spring polymer model of the replicating C. crescentus chromosome, we model transient ParA-ParB contacts that generate DNA loops and an effective entropic repulsion. This repulsion drives chromosome segregation and produces oriC trajectories consistent with experiments, aided by the ParA concentration gradient near the new pole. This minimal framework, incorporating the physics of topologically modified (ToMo) polymers, allows us to quantitatively reproduce the time-dependent spatial organization of different tagged loci and replisomes observed in multiple experiments. Incorporating a minimal model of extrusion also allows us to recover the linear arrangement of the chromosome arms, as is inferred from the characteristic diagonals of Hi-C maps.
