Single-Molecule Imaging Reveals a Collapsed Conformational State for DNA-Bound Cohesin

Cell Rep. 2016 May 3;15(5):988-998. doi: 10.1016/j.celrep.2016.04.003. Epub 2016 Apr 21.


Cohesin is essential for the hierarchical organization of the eukaryotic genome and plays key roles in many aspects of chromosome biology. The conformation of cohesin bound to DNA remains poorly defined, leaving crucial gaps in our understanding of how cohesin fulfills its biological functions. Here, we use single-molecule microscopy to directly observe the dynamic and functional characteristics of cohesin bound to DNA. We show that cohesin can undergo rapid one-dimensional (1D) diffusion along DNA, but individual nucleosomes, nucleosome arrays, and other protein obstacles significantly restrict its mobility. Furthermore, we demonstrate that DNA motor proteins can readily push cohesin along DNA, but they cannot pass through the interior of the cohesin ring. Together, our results reveal that DNA-bound cohesin has a central pore that is substantially smaller than anticipated. These findings have direct implications for understanding how cohesin and other SMC proteins interact with and distribute along chromatin.

Publication types

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

MeSH terms

  • AT Rich Sequence / genetics
  • Base Sequence
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / chemistry*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA / metabolism*
  • Diffusion
  • Models, Biological
  • Molecular Motor Proteins / metabolism
  • Nucleosomes / metabolism
  • Porosity
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / chemistry*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Single Molecule Imaging / methods*


  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Molecular Motor Proteins
  • Nucleosomes
  • Schizosaccharomyces pombe Proteins
  • cohesins
  • DNA