Borealin-nucleosome interaction secures chromosome association of the chromosomal passenger complex

J Cell Biol. 2019 Dec 2;218(12):3912-3925. doi: 10.1083/jcb.201905040. Epub 2019 Sep 30.

Abstract

Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres, failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding. Disrupting Borealin-nucleosome interactions excluded the CPC from chromosomes and caused chromosome congression defects. We also show that Borealin-mediated chromosome association of the CPC is critical for Haspin- and Bub1-mediated centromere enrichment of the CPC and works upstream of the latter. Our work thus establishes Borealin as a master regulator determining the chromosome association and function of the CPC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase B / metabolism
  • Cell Cycle Proteins / metabolism*
  • Cell Division
  • Centromere / ultrastructure
  • Chromosome Segregation
  • Chromosomes / metabolism*
  • HeLa Cells
  • Histones / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kinetics
  • Mass Spectrometry
  • Microscopy, Fluorescence
  • Mitosis
  • Nucleosomes / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protein Folding
  • Protein-Serine-Threonine Kinases / metabolism
  • Recombinant Proteins / metabolism
  • Survivin / metabolism
  • Xenopus laevis

Substances

  • BIRC5 protein, human
  • CDCA8 protein, human
  • Cell Cycle Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Nucleosomes
  • Recombinant Proteins
  • Survivin
  • Aurora Kinase B
  • BUB1 protein, human
  • HASPIN protein, human
  • Protein-Serine-Threonine Kinases

Associated data

  • PDB/1KX5
  • PDB/2QFA
  • PDB/2KDD