The spatial segregation of pericentric cohesin and condensin in the mitotic spindle

Mol Biol Cell. 2013 Dec;24(24):3909-19. doi: 10.1091/mbc.E13-06-0325. Epub 2013 Oct 23.

Abstract

In mitosis, the pericentromere is organized into a spring composed of cohesin, condensin, and a rosette of intramolecular chromatin loops. Cohesin and condensin are enriched in the pericentromere, with spatially distinct patterns of localization. Using model convolution of computer simulations, we deduce the mechanistic consequences of their spatial segregation. Condensin lies proximal to the spindle axis, whereas cohesin is radially displaced from condensin and the interpolar microtubules. The histone deacetylase Sir2 is responsible for the axial position of condensin, while the radial displacement of chromatin loops dictates the position of cohesin. The heterogeneity in distribution of condensin is most accurately modeled by clusters along the spindle axis. In contrast, cohesin is evenly distributed (barrel of 500-nm width × 550-nm length). Models of cohesin gradients that decay from the centromere or sister cohesin axis, as previously suggested, do not match experimental images. The fine structures of cohesin and condensin deduced with subpixel localization accuracy reveal critical features of how these complexes mold pericentric chromatin into a functional spring.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Centromere / genetics
  • Chromatin / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cohesins
  • Computer Simulation
  • DNA-Binding Proteins / metabolism*
  • Kinetochores
  • Microtubules
  • Mitosis / genetics*
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / genetics
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Sirtuin 2 / genetics
  • Spindle Apparatus / genetics*

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • condensin complexes
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Adenosine Triphosphatases