Shugoshin collaborates with protein phosphatase 2A to protect cohesin

Nature. 2006 May 4;441(7089):46-52. doi: 10.1038/nature04663. Epub 2006 Mar 15.

Abstract

Sister chromatid cohesion, mediated by a complex called cohesin, is crucial--particularly at centromeres--for proper chromosome segregation in mitosis and meiosis. In animal mitotic cells, phosphorylation of cohesin promotes its dissociation from chromosomes, but centromeric cohesin is protected by shugoshin until kinetochores are properly captured by the spindle microtubules. However, the mechanism of shugoshin-dependent protection of cohesin is unknown. Here we find a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. Purified shugoshin complex has an ability to reverse the phosphorylation of cohesin in vitro, suggesting that dephosphorylation of cohesin is the mechanism of protection at centromeres. Meiotic shugoshin of fission yeast also associates with PP2A, with both proteins collaboratively protecting Rec8-containing cohesin at centromeres. Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism*
  • Chromatids / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Pairing*
  • HeLa Cells
  • Humans
  • Meiosis
  • Mitosis
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism*
  • Phosphoprotein Phosphatases / classification
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Phosphatase 2
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Multiprotein Complexes
  • Nuclear Proteins
  • Phosphoproteins
  • SGO1 protein, human
  • SGOL2 protein, human
  • Schizosaccharomyces pombe Proteins
  • cohesins
  • REC8 protein, S pombe
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2