Condensin association with histone H2A shapes mitotic chromosomes

Nature. 2011 Jun 1;474(7352):477-83. doi: 10.1038/nature10179.

Abstract

Chromosome structure is dynamically regulated during cell division, and this regulation is dependent, in part, on condensin. The localization of condensin at chromosome arms is crucial for chromosome partitioning during anaphase. Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear. Here we show that fission yeast (Schizosaccharomyces pombe) kinetochore proteins Pcs1 and Mde4--homologues of budding yeast (Saccharomyces cerevisiae) monopolin subunits and known to prevent merotelic kinetochore orientation--act as a condensin 'recruiter' at kinetochores, and that condensin itself may act to clamp microtubule binding sites during metaphase. In addition to the regional recruitment factors, overall condensin association with chromatin is governed by the chromosomal passenger kinase Aurora B. Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin 'receptors' of condensin. Condensin phosphorylation and its deposition onto chromosome arms reach a peak during anaphase, when Aurora B kinase relocates from centromeres to the spindle midzone, where the separating chromosome arms are positioned. Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Aurora Kinase B
  • Aurora Kinases
  • Binding Sites
  • Cell Cycle Proteins / metabolism
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes, Fungal / metabolism*
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Kinetochores / metabolism
  • Microtubules / metabolism
  • Mitosis*
  • Multiprotein Complexes / metabolism*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / metabolism*
  • Schizosaccharomyces pombe Proteins / metabolism
  • cdc25 Phosphatases / genetics
  • cdc25 Phosphatases / metabolism

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Cnd2 protein, S pombe
  • DNA-Binding Proteins
  • Histones
  • Mde4 protein, S pombe
  • Multiprotein Complexes
  • NCAPH protein, human
  • Nuclear Proteins
  • Pcs1 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • condensin complexes
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • ark1 protein, S pombe
  • cdc25 Phosphatases
  • Adenosine Triphosphatases