Borealin dimerization mediates optimal CPC checkpoint function by enhancing localization to centromeres and kinetochores

Nat Commun. 2015 Apr 9;6:6775. doi: 10.1038/ncomms7775.

Abstract

The chromosomal passenger complex (CPC) localizes to centromeres where it activates the mitotic checkpoint in response to inappropriate inter-kinetochore tension. This error correction function is essential for proper chromosome segregation. Here we define several critical features of CPC localization and function. First, the Borealin dimerization domain suppresses dynamic exchange at the centromere to allow optimal CPC function. Second, Borealin dimerization is essential to target a subpopulation of CPC proximal to the kinetochore when the mitotic spindle is disrupted. This subpopulation is also needed for full CPC checkpoint function. The existence of a pool of CPC at the kinetochore suggests that error correction is more complicated than predicted from the Aurora B phosphorylation gradient model. Finally, Haspin kinase plays a key role in maintaining the slowly exchanging centromere Borealin pool, while Aurora B and Mps1 play minimal roles in maintaining CPC localization once cells are in mitosis.

Publication types

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

MeSH terms

  • Aurora Kinase B / metabolism
  • Blotting, Western
  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism
  • Chromosome Segregation*
  • Flow Cytometry
  • Fluorescence Recovery After Photobleaching
  • HeLa Cells
  • Histone Code
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetochores / metabolism*
  • M Phase Cell Cycle Checkpoints*
  • Microscopy, Fluorescence
  • Protein Multimerization*
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism

Substances

  • CDCA8 protein, human
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein-Tyrosine Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • HASPIN protein, human
  • Protein-Serine-Threonine Kinases
  • TTK protein, human