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Cell Reports· 2025Q1

Cohesin supercoils DNA during loop extrusion

Iain F. Davidson, Roman Barth, Kota Nagasaka, Wen Tang et al.

Short summary

Cohesin negatively supercoils DNA during loop extrusion, a process requiring ATPase head engagement, DNA clamping, and a hinge binding site.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Cohesin negatively supercoils DNA during loop extrusion.
  • Supercoiling mechanism involves ATPase head engagement, DNA clamping, and hinge binding.
  • A cohesin mutant defective in supercoiling forms shorter DNA loops.
  • Topoisomerase I depletion shows a similar, weaker phenotype.

AI-generated from the title and abstract; the full text is not read.

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.

The authors' abstract, as published at the source. Cell Reports, 2025 · DOI ↗

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Field: Molecular Biology

Molecular BiologyBiochemistry, Genetics and Molecular Biology