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Human cohesin compacts DNA by loop extrusion

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Science  13 Dec 2019:
Vol. 366, Issue 6471, pp. 1345-1349
DOI: 10.1126/science.aaz4475

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Cohesin extrudes DNA loops

DNA is folded into loops in eukaryotic cells by a process that depends on a ring-shaped adenosine triphosphatase complex called cohesin. Davidson et al. and Kim et al. now show that in the presence of the NIPBLMAU2 protein complex, the human cohesin complex can function as a molecular motor that extrudes DNA loops with high speed in vitro. In contrast to how it mediates sister chromatid cohesion, cohesin does not appear to entrap DNA topologically during loop extrusion. The results provide direct evidence for the loop extrusion model of chromatin organization and suggest that genome architecture is highly dynamic.

Science, this issue p. 1338, p. 1345

Abstract

Cohesin is a chromosome-bound, multisubunit adenosine triphosphatase complex. After loading onto chromosomes, it generates loops to regulate chromosome functions. It has been suggested that cohesin organizes the genome through loop extrusion, but direct evidence is lacking. Here, we used single-molecule imaging to show that the recombinant human cohesin-NIPBL complex compacts both naked and nucleosome-bound DNA by extruding DNA loops. DNA compaction by cohesin requires adenosine triphosphate (ATP) hydrolysis and is force sensitive. This compaction is processive over tens of kilobases at an average rate of 0.5 kilobases per second. Compaction of double-tethered DNA suggests that a cohesin dimer extrudes DNA loops bidirectionally. Our results establish cohesin-NIPBL as an ATP-driven molecular machine capable of loop extrusion.

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