Deprotection of centromeric cohesin at meiosis II requires APC/C activity but not kinetochore tension

EMBO J. 2021 Apr 1;40(7):e106812. doi: 10.15252/embj.2020106812. Epub 2021 Mar 1.

Abstract

Genome haploidization involves sequential loss of cohesin from chromosome arms and centromeres during two meiotic divisions. At centromeres, cohesin's Rec8 subunit is protected from separase cleavage at meiosis I and then deprotected to allow its cleavage at meiosis II. Protection of centromeric cohesin by shugoshin-PP2A seems evolutionarily conserved. However, deprotection has been proposed to rely on spindle forces separating the Rec8 protector from cohesin at metaphase II in mammalian oocytes and on APC/C-dependent destruction of the protector at anaphase II in yeast. Here, we have activated APC/C in the absence of sister kinetochore biorientation at meiosis II in yeast and mouse oocytes, and find that bipolar spindle forces are dispensable for sister centromere separation in both systems. Furthermore, we show that at least in yeast, protection of Rec8 by shugoshin and inhibition of separase by securin are both required for the stability of centromeric cohesin at metaphase II. Our data imply that related mechanisms preserve the integrity of dyad chromosomes during the short metaphase II of yeast and the prolonged metaphase II arrest of mammalian oocytes.

Keywords: biorientation; centromeric cohesion; meiosis II; protection; shugoshin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • Cell Cycle Proteins / metabolism*
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Female
  • Kinetochores / metabolism*
  • Meiosis*
  • Mice
  • Oocytes / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • REC8 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • cohesins
  • Anaphase-Promoting Complex-Cyclosome