Inner centromere localization of the CPC maintains centromere cohesion and allows mitotic checkpoint silencing

Nat Commun. 2017 May 31:8:15542. doi: 10.1038/ncomms15542.

Abstract

Faithful chromosome segregation during mitosis requires that the kinetochores of all sister chromatids become stably connected to microtubules derived from opposite spindle poles. How stable chromosome bi-orientation is accomplished and coordinated with anaphase onset remains incompletely understood. Here we show that stable chromosome bi-orientation requires inner centromere localization of the non-enzymatic subunits of the chromosomal passenger complex (CPC) to maintain centromeric cohesion. Precise inner centromere localization of the CPC appears less relevant for Aurora B-dependent resolution of erroneous kinetochore-microtubule (KT-MT) attachments and for the stabilization of bi-oriented KT-MT attachments once sister chromatid cohesion is preserved via knock-down of WAPL. However, Aurora B inner centromere localization is essential for mitotic checkpoint silencing to allow spatial separation from its kinetochore substrate KNL1. Our data infer that the CPC is localized at the inner centromere to sustain centromere cohesion on bi-oriented chromosomes and to coordinate mitotic checkpoint silencing with chromosome bi-orientation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Aurora Kinase B / metabolism*
  • Cell Cycle Proteins / metabolism
  • Centromere / ultrastructure*
  • Chromatids / metabolism
  • Chromosome Segregation
  • Chromosomes / metabolism
  • Gene Silencing
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • M Phase Cell Cycle Checkpoints
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Mitosis*
  • Phosphorylation
  • RNA, Small Interfering / metabolism
  • Spindle Apparatus / metabolism

Substances

  • Cell Cycle Proteins
  • Knl1 protein, human
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • AURKB protein, human
  • Aurora Kinase B