Cohesin supercoils DNA during loop extrusion.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-06-13 DOI:10.1016/j.celrep.2025.115856

Iain F Davidson, Roman Barth, Kota Nagasaka, Wen Tang, Gordana Wutz, Sabrina Horn, Richard Janissen, Roman R Stocsits, Emilia Chlosta, Benedikt W Bauer, Cees Dekker, Jan-Michael Peters

引用次数: 0

Abstract

Cohesin extrudes genomic DNA into loops that promote chromatin assembly, gene regulation, and gene recombination. Loop extrusion depends on large-scale conformational changes in cohesin, but how these translocate DNA is poorly understood. Here, we provide evidence that cohesin negatively supercoils DNA during loop extrusion. Supercoiling requires the engagement of cohesin's ATPase heads, DNA clamping by these heads, and a DNA-binding site on cohesin's hinge, indicating that cohesin twists DNA when constraining it between the hinge and the clamp. A cohesin mutant defective in negative supercoiling forms shorter loops in cells, and a similar, although weaker, phenotype is observed after the depletion of topoisomerase I. These results suggest that supercoiling is an integral part of the loop-extrusion mechanism and that relaxation of supercoiled DNA is required for cohesin-mediated loop extrusion and genome architecture.

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环挤压过程中的内聚蛋白超螺旋DNA。

内聚蛋白将基因组DNA挤压成环，促进染色质组装、基因调控和基因重组。环挤压依赖于内聚蛋白的大规模构象变化，但人们对这些DNA易位的机制知之甚少。在这里，我们提供证据，内聚蛋白负超圈DNA在环挤压。超卷曲需要内聚蛋白的atp酶头参与，DNA被这些头夹住，以及内聚蛋白铰链上的DNA结合位点，这表明当内聚蛋白将DNA束缚在铰链和夹子之间时，它会扭曲DNA。负超卷曲缺陷的粘聚蛋白突变体在细胞中形成较短的环，并且在拓扑异构酶i耗尽后观察到类似但较弱的表型。这些结果表明，超卷曲是环挤压机制的一个组成部分，并且超卷曲DNA的松弛是粘聚蛋白介导的环挤压和基因组结构所必需的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.