APC/C Cdh1 Enables Removal of Shugoshin-2 from the Arms of Bivalent Chromosomes by Moderating Cyclin-Dependent Kinase Activity

Curr Biol. 2017 May 22;27(10):1462-1476.e5. doi: 10.1016/j.cub.2017.04.023. Epub 2017 May 11.

Abstract

In mammalian females, germ cells remain arrested as primordial follicles. Resumption of meiosis is heralded by germinal vesicle breakdown, condensation of chromosomes, and their eventual alignment on metaphase plates. At the first meiotic division, anaphase-promoting complex/cyclosome associated with Cdc20 (APC/CCdc20) activates separase and thereby destroys cohesion along chromosome arms. Because cohesion around centromeres is protected by shugoshin-2, sister chromatids remain attached through centromeric/pericentromeric cohesin. We show here that, by promoting proteolysis of cyclins and Cdc25B at the germinal vesicle (GV) stage, APC/C associated with the Cdh1 protein (APC/CCdh1) delays the increase in Cdk1 activity, leading to germinal vesicle breakdown (GVBD). More surprisingly, by moderating the rate at which Cdk1 is activated following GVBD, APC/CCdh1 creates conditions necessary for the removal of shugoshin-2 from chromosome arms by the Aurora B/C kinase, an event crucial for the efficient resolution of chiasmata.

Keywords: APC/C(Cdh1); aneuploidy; aurora kinase; cohesin; meiosis; shugoshin-2.

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome / metabolism
  • Aurora Kinase B / metabolism
  • Aurora Kinase C / metabolism
  • CDC2 Protein Kinase / metabolism
  • Cdc20 Proteins / physiology
  • Cdh1 Proteins / metabolism
  • Cell Cycle Proteins / metabolism*
  • Centromere
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosomes*
  • Female
  • Germinal Center
  • Male
  • Meiosis*
  • Mice
  • Mice, Knockout
  • Models, Theoretical
  • Separase / metabolism
  • cdc25 Phosphatases / physiology

Substances

  • Cdc20 Proteins
  • Cdc20 protein, mouse
  • Cdh1 Proteins
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fzr1 protein, mouse
  • SGOL2 protein, mouse
  • cohesins
  • Anapc2 protein, mouse
  • Anaphase-Promoting Complex-Cyclosome
  • Apc2 Subunit, Anaphase-Promoting Complex-Cyclosome
  • Aurkb protein, mouse
  • Aurkc protein, mouse
  • Aurora Kinase B
  • Aurora Kinase C
  • CDC2 Protein Kinase
  • cdc25 Phosphatases
  • Separase