Compaction and segregation of sister chromatids via active loop extrusion

Elife. 2016 May 18;5:e14864. doi: 10.7554/eLife.14864.

Abstract

The mechanism by which chromatids and chromosomes are segregated during mitosis and meiosis is a major puzzle of biology and biophysics. Using polymer simulations of chromosome dynamics, we show that a single mechanism of loop extrusion by condensins can robustly compact, segregate and disentangle chromosomes, arriving at individualized chromatids with morphology observed in vivo. Our model resolves the paradox of topological simplification concomitant with chromosome 'condensation', and explains how enzymes a few nanometers in size are able to control chromosome geometry and topology at micron length scales. We suggest that loop extrusion is a universal mechanism of genome folding that mediates functional interactions during interphase and compacts chromosomes during mitosis.

Keywords: biophysics; chromosome; chromosomes; compaction; genes; molecular dynamics; none; polymer; simulations; structural biology.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Chromatids / metabolism*
  • Chromosome Segregation*
  • Computer Simulation
  • DNA Replication*
  • DNA-Binding Proteins / metabolism
  • Meiosis*
  • Mitosis*
  • Models, Biological
  • Multiprotein Complexes / metabolism

Substances

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