Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I

Nat Commun. 2017 Sep 25;8(1):694. doi: 10.1038/s41467-017-00774-3.

Abstract

A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / metabolism*
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Meiosis / physiology*
  • Mice
  • Oocytes / cytology*
  • Oocytes / metabolism
  • Oocytes / ultrastructure
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • SGO2 protein, mouse
  • cohesins
  • Ttk protein, mouse
  • Bub1 protein, mouse
  • Protein-Serine-Threonine Kinases