All eukaryotic SMC proteins induce a twist of -0.6 at each DNA loop extrusion step

Sci Adv. 2024 Dec 13;10(50):eadt1832. doi: 10.1126/sciadv.adt1832. Epub 2024 Dec 13.

Abstract

Eukaryotes carry three types of structural maintenance of chromosome (SMC) protein complexes, condensin, cohesin, and SMC5/6, which are ATP-dependent motor proteins that remodel the genome via DNA loop extrusion (LE). SMCs modulate DNA supercoiling but remains incompletely understood how this is achieved. Using a single-molecule magnetic tweezers assay that directly measures how much twist is induced by individual SMCs in each LE step, we demonstrate that all three SMC complexes induce the same large negative twist (i.e., linking number change [Formula: see text] of ~-0.6 at each LE step) into the extruded loop, independent of step size and DNA tension. Using ATP hydrolysis mutants and nonhydrolyzable ATP analogs, we find that ATP binding is the twist-inducing event during the ATPase cycle, coinciding with the force-generating LE step. The fact that all three eukaryotic SMC proteins induce the same amount of twist indicates a common DNA-LE mechanism among these SMC complexes.

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Cell Cycle Proteins* / chemistry
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Chromosomal Proteins, Non-Histone* / chemistry
  • Chromosomal Proteins, Non-Histone* / metabolism
  • Cohesins
  • DNA / chemistry
  • DNA / metabolism
  • DNA, Superhelical / chemistry
  • DNA, Superhelical / metabolism
  • DNA-Binding Proteins* / chemistry
  • DNA-Binding Proteins* / metabolism
  • Eukaryota / metabolism
  • Multiprotein Complexes* / chemistry
  • Multiprotein Complexes* / metabolism
  • Nucleic Acid Conformation

Substances

  • Chromosomal Proteins, Non-Histone
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Adenosine Triphosphatases
  • Adenosine Triphosphate
  • DNA
  • condensin complexes
  • Cohesins
  • DNA, Superhelical