Condensin-driven loop extrusion on supercoiled DNA

Nat Struct Mol Biol. 2022 Jul;29(7):719-727. doi: 10.1038/s41594-022-00802-x. Epub 2022 Jul 14.

Abstract

Condensin, a structural maintenance of chromosomes (SMC) complex, has been shown to be a molecular motor protein that organizes chromosomes by extruding loops of DNA. In cells, such loop extrusion is challenged by many potential conflicts, for example, the torsional stresses that are generated by other DNA-processing enzymes. It has so far remained unclear how DNA supercoiling affects loop extrusion. Here, we use time-lapse single-molecule imaging to study condensin-driven DNA loop extrusion on supercoiled DNA. We find that condensin binding and DNA looping are stimulated by positively supercoiled DNA, and condensin preferentially binds near the tips of supercoiled plectonemes. Upon loop extrusion, condensin collects nearby plectonemes into a single supercoiled loop that is highly stable. Atomic force microscopy imaging shows that condensin generates supercoils in the presence of ATP. Our findings provide insight into the topology-regulated loading and formation of supercoiled loops by SMC complexes and clarify the interplay of loop extrusion and supercoiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases* / metabolism
  • Cell Cycle Proteins / metabolism
  • DNA / metabolism
  • DNA, Superhelical*
  • DNA-Binding Proteins
  • Multiprotein Complexes / chemistry

Substances

  • Cell Cycle Proteins
  • DNA, Superhelical
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • condensin complexes
  • DNA
  • Adenosine Triphosphatases