The spatial organization of chromosomes by structural maintenance of chromosomes (SMC) complexes is vital to organisms from bacteria to humans. SMC complexes were recently found to be motors that extrude DNA loops. It remains unclear, however, what happens when multiple SMC complexes encounter one another in vivo on the same DNA, how encounters are resolved, or how interactions help organize an active genome. Here, we set up a crash-course track system to study what happens when SMC complexes encounter one another. Using the parS/ParB system, which loads SMC complexes in a targeted manner, we engineered the Bacillus subtilis chromosome to have multiple SMC loading sites. Chromosome conformation capture (Hi-C) analyses of over 20 engineered strains show an amazing variety of never-before-seen chromosome folding patterns. Polymer simulations indicate these patterns require SMC complexes to traverse past each other in vivo, contrary to the common assumption that SMC complexes mutually block each others extrusion activity. Our quantitative model of bypassing predicted that increasing the numbers of SMCs on the chromosome could overwhelm the bypassing mechanism, create SMC traffic jams, and lead to major chromosome reorganization. We validated these predictions experimentally. We posit that SMC complexes traversing one another is part of a larger phenomenon of bypassing large steric barriers which enables these loop extruders to spatially organize a functional and busy genome.

中文翻译：

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DNA环挤出SMC复合物可在体内相互穿越

通过染色体（SMC）复合物的结构维护来实现染色体的空间组织对于从细菌到人类的生物至关重要。最近发现SMC复合物是挤压DNA环的马达。但是，目前还不清楚当多个SMC复合物在同一DNA上在体内相互遇到时，会如何解决，或者如何相互作用帮助组织一个活跃的基因组，会发生什么。在这里，我们建立了一个碰撞过程跟踪系统，以研究SMC复合体彼此相遇时发生的情况。使用以有针对性的方式加载SMC复合物的parS / ParB系统，我们将枯草芽孢杆菌染色体改造为具有多个SMC加载位点。超过20种工程菌株的染色体构象捕获（Hi-C）分析显示了前所未有的惊人的染色体折叠模式。聚合物模拟表明，这些模式需要SMC配合物在体内相互越过，这与SMC配合物相互阻碍彼此的挤出活性这一普遍假设相反。我们的绕过定量模型预测，增加染色体上SMC的数量可能会使绕过机理不堪重负，造成SMC交通堵塞，并导致主要的染色体重组。我们通过实验验证了这些预测。我们认为，SMC络合物相互穿越是绕过大型空间障碍的一种较大现象的一部分，该现象使这些环挤出机能够在空间上组织一个功能繁忙的基因组。我们的绕过定量模型预测，增加染色体上SMC的数量可能会使绕过机理不堪重负，造成SMC交通堵塞，并导致主要的染色体重组。我们通过实验验证了这些预测。我们认为，SMC络合物相互穿越是绕过大型空间障碍的一种较大现象的一部分，该现象使这些环挤出机能够在空间上组织一个功能繁忙的基因组。我们的绕过定量模型预测，增加染色体上SMC的数量可能会使绕过机理不堪重负，造成SMC交通堵塞，并导致主要的染色体重组。我们通过实验验证了这些预测。我们认为，SMC络合物相互穿越是绕过大型空间障碍的一种较大现象的一部分，该现象使这些环挤出机能够在空间上组织一个功能繁忙的基因组。