Human cohesin compacts DNA by loop extrusion

Science. 2019 Dec 13;366(6471):1345-1349. doi: 10.1126/science.aaz4475. Epub 2019 Nov 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry*
  • Chromosomal Proteins, Non-Histone / chemistry*
  • DNA / chemistry*
  • Humans
  • Nucleic Acid Conformation*
  • Nucleosomes / chemistry
  • Protein Multimerization
  • Proton-Translocating ATPases / chemistry*
  • Single Molecule Imaging

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • NIPBL protein, human
  • Nucleosomes
  • cohesins
  • DNA
  • Proton-Translocating ATPases