title: Bub1 kinase and Sgo1 modulate pericentric chromatin in response to altered microtubule dynamics.
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.
authors.affiliation: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3280, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Haase
authors.forename: Andrew
authors.initials: A
authors.lastname: Stephens
authors.forename: Jolien
authors.initials: J
authors.lastname: Verdaasdonk
authors.forename: Elaine
authors.initials: E
authors.lastname: Yeh
authors.forename: Kerry
authors.initials: K
authors.lastname: Bloom
mesh_terms: D001542:Benomyl / Q000494:pharmacology; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism*; D004271:DNA, Fungal / Q000737:chemistry / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D002843:Chromatin; D004271:DNA, Fungal; D006657:Histones; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C482640:Sgo1 protein, S cerevisiae; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D001542:Benomyl