The juxtaposition of intracellular DNA segments, together with the DNA‐passage activity of topoisomerase II, leads to the formation of DNA knots and interlinks, which jeopardize chromatin structure and gene expression. Recent studies in budding yeast have shown that some mechanism minimizes the knotting probability of intracellular DNA. Here, we tested whether this is achieved via the intrinsic capacity of topoisomerase II for simplifying the equilibrium topology of DNA; or whether it is mediated by SMC (structural maintenance of chromosomes) protein complexes like condensin or cohesin, whose capacity to extrude DNA loops could enforce dissolution of DNA knots by topoisomerase II. We show that the low knotting probability of DNA does not depend on the simplification capacity of topoisomerase II nor on the activities of cohesin or Smc5/6 complexes. However, inactivation of condensin increases the occurrence of DNA knots throughout the cell cycle. These results suggest an in vivo role for the DNA loop extrusion activity of condensin and may explain why condensin disruption produces a variety of alterations in interphase chromatin, in addition to persistent sister chromatid interlinks in mitotic chromatin.

中文翻译：

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Condensin 最大限度地减少体内拓扑异构酶 II 介导的 DNA 缠结


细胞内 DNA 片段的并置以及拓扑异构酶 II 的 DNA 传代活性导致 DNA 结和互连的形成，从而危及染色质结构和基因表达。最近对芽殖酵母的研究表明，某些机制可以最大限度地减少细胞内 DNA 的打结概率。在这里，我们测试了这是否是通过拓扑异构酶 II 简化 DNA 平衡拓扑的内在能力来实现的；或者它是否是由 SMC（染色体结构维持）蛋白质复合物介导的，例如凝缩蛋白或粘连蛋白，其挤出 DNA 环的能力可以通过拓扑异构酶 II 强制溶解 DNA 结。我们证明 DNA 的低打结概率不依赖于拓扑异构酶 II 的简化能力，也不依赖于粘连蛋白或 Smc5/6 复合物的活性。然而，凝缩蛋白的失活会增加整个细胞周期中 DNA 结的出现。这些结果表明凝缩蛋白的 DNA 环挤出活性在体内发挥作用，并且可以解释为什么除了有丝分裂染色质中持久的姐妹染色单体互连之外，凝缩蛋白破坏还会在间期染色质中产生各种改变。