Journal
EMBO JOURNAL
Volume 40, Issue 7, Pages -Publisher
WILEY
DOI: 10.15252/embj.2020106812
Keywords
biorientation; centromeric cohesion; meiosis II; protection; shugoshin
Categories
Funding
- Max Planck Society
- European Union's (EU) Horizon 2020 research and innovation program [634113]
- Projekt DEAL
- H2020 Societal Challenges Programme [634113] Funding Source: H2020 Societal Challenges Programme
- MRC [1797416] Funding Source: UKRI
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This study explores the mechanisms of genome haploidization involving cohesin protection and deprotection at centromeres during meiotic divisions. It is found that APC/C activation can lead to sister centromere separation without bipolar spindle forces in yeast and mouse oocytes. Additionally, the stability of centromeric cohesin at metaphase II requires both Rec8 protection by shugoshin and separase inhibition by securin in yeast. These findings suggest that similar mechanisms preserve chromosome integrity during metaphase II in yeast and prolonged metaphase II arrest in mammalian oocytes.
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.
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