Sds22 and Repo-Man stabilize chromosome segregation by counteracting Aurora B on anaphase kinetochores

J Cell Biol. 2012 Jul 23;198(2):173-83. doi: 10.1083/jcb.201112112. Epub 2012 Jul 16.

Abstract

During mitotic spindle assembly, Aurora B kinase is part of an error correction mechanism that detaches microtubules from kinetochores that are under low mechanical tension. During anaphase, however, kinetochore-microtubule attachments must be maintained despite a drop of tension after removal of sister chromatid cohesion. Consistent with this requirement, Aurora B relocates away from chromosomes to the central spindle at the metaphase-anaphase transition. By ribonucleic acid interference screening using a phosphorylation biosensor, we identified two PP1-targeting subunits, Sds22 and Repo-Man, which counteracted Aurora B-dependent phosphorylation of the outer kinetochore component Dsn1 during anaphase. Sds22 or Repo-Man depletion induced transient pauses during poleward chromosome movement and a high incidence of chromosome missegregation. Thus, our study identifies PP1-targeting subunits that regulate the microtubule-kinetochore interface during anaphase for faithful chromosome segregation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase*
  • Aurora Kinase B
  • Aurora Kinases
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation*
  • HeLa Cells
  • Humans
  • Kinetochores / metabolism*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Protein Phosphatase 1 / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Spindle Apparatus / metabolism

Substances

  • CDCA2 protein, human
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DSN1 protein, human
  • Nuclear Proteins
  • PPP1R7 protein, human
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Protein Phosphatase 1