Bub1 kinase and Sgo1 modulate pericentric chromatin in response to altered microtubule dynamics

Curr Biol. 2012 Mar 20;22(6):471-81. doi: 10.1016/j.cub.2012.02.006. Epub 2012 Feb 23.

Abstract

Background: Tension sensing of bioriented chromosomes is essential for the fidelity of chromosome segregation. The spindle assembly checkpoint (SAC) conveys lack of tension or attachment to the anaphase promoting complex. Components of the SAC (Bub1) phosphorylate histone H2A (S121) and recruit the protector of cohesin, Shugoshin (Sgo1), to the inner centromere. How the chromatin structural modifications of the inner centromere are integrated into the tension sensing mechanisms and the checkpoint are not known.

Results: We have identified a Bub1/Sgo1-dependent structural change in the geometry and dynamics of kinetochores and the pericentric chromatin upon reduction of microtubule dynamics. The cluster of inner kinetochores contract, whereas the pericentric chromatin and cohesin that encircle spindle microtubules undergo a radial expansion. Despite its increased spatial distribution, the pericentric chromatin is less dynamic. The change in dynamics is due to histone H2A phosphorylation and Sgo1 recruitment to the pericentric chromatin, rather than microtubule dynamics.

Conclusions: Bub1 and Sgo1 act as a rheostat to regulate the chromatin spring and maintain force balance. Through histone H2A S121 phosphorylation and recruitment of Sgo1, Bub1 kinase softens the chromatin spring in response to changes in microtubule dynamics. The geometric alteration of all 16 kinetochores and pericentric chromatin reflect global changes in the pericentromeric region and provide mechanisms for mechanically amplifying damage at a single kinetochore microtubule.

Publication types

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

MeSH terms

  • Benomyl / pharmacology
  • Centromere / metabolism
  • Chromatin / metabolism*
  • DNA, Fungal / chemistry
  • DNA, Fungal / metabolism
  • Histones / metabolism
  • Kinetochores / metabolism
  • Microtubules / metabolism*
  • Models, Biological
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stress, Mechanical

Substances

  • Chromatin
  • DNA, Fungal
  • Histones
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Sgo1 protein, S cerevisiae
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases
  • Benomyl