Theory and simulations of condensin mediated loop extrusion in DNA

Nat Commun. 2021 Oct 7;12(1):5865. doi: 10.1038/s41467-021-26167-1.

Abstract

Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Bacteria / genetics
  • Chromatin
  • Chromosomes / metabolism
  • DNA / chemistry
  • DNA / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Genetic Techniques
  • Humans
  • Kinetics
  • Models, Genetic
  • Multiprotein Complexes / metabolism*
  • Transcription, Genetic

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • condensin complexes
  • DNA
  • Adenosine Triphosphatases