ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin

Mol Biol Cell. 2016 Jan 1;27(1):153-66. doi: 10.1091/mbc.E15-08-0575. Epub 2015 Nov 4.

Abstract

ChromoShake is a three-dimensional simulator designed to find the thermodynamically favored states for given chromosome geometries. The simulator has been applied to a geometric model based on experimentally determined positions and fluctuations of DNA and the distribution of cohesin and condensin in the budding yeast centromere. Simulations of chromatin in differing initial configurations reveal novel principles for understanding the structure and function of a eukaryotic centromere. The entropic position of DNA loops mirrors their experimental position, consistent with their radial displacement from the spindle axis. The barrel-like distribution of cohesin complexes surrounding the central spindle in metaphase is a consequence of the size of the DNA loops within the pericentromere to which cohesin is bound. Linkage between DNA loops of different centromeres is requisite to recapitulate experimentally determined correlations in DNA motion. The consequences of radial loops and cohesin and condensin binding are to stiffen the DNA along the spindle axis, imparting an active function to the centromere in mitosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / chemistry*
  • Centromere / genetics
  • Centromere / metabolism
  • Chromatin / chemistry*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Cohesins
  • Computer Simulation
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Kinetochores / chemistry
  • Kinetochores / metabolism
  • Microtubules / metabolism
  • Models, Genetic*
  • Molecular Dynamics Simulation*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Saccharomycetales / chemistry
  • Saccharomycetales / genetics
  • Saccharomycetales / metabolism
  • Spindle Apparatus / metabolism
  • Structure-Activity Relationship
  • Thermodynamics

Substances

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