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Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes

Abstract : To generate haploid gametes, cohesin is removed in a step-wise manner from chromosome arms in meiosis I and the centromere region in meiosis II, to segregate chromosomes and sister chromatids, respectively. Meiotic cohesin removal requires cleavage of the meiosis-specific kleisin subunit Rec8 by the protease Separase 1,2. In yeast and C. elegans, Rec8 on chromosome arms has to be phosphorylated to be cleaved in meiosis I 3-7 , whereas Rec8 at the centromere is protected from cleavage by the action of PP2A-B56 8-10. However, in mammalian meiosis it is unknown whether Rec8 has to be equally phosphorylated for cleavage, and if so, the identity of the relevant kinase(s). This is due to technical challenges, as Rec8 is poorly conserved preventing a direct translation of the knowledge gained from model systems such as yeast and C. elegans to mammals. Additionally, there is no turnover of Rec8 after cohesion establishment, preventing phosphomutant analysis of functional Rec8. To address the very basic question of whether Rec8 cleavage requires its phosphorylation in mammals, we adapted a biosensor detecting Separase activity to study Rec8 cleavage in single mouse oocytes by live imaging. Crucially, through phosphomutant analysis we identified phosphorylation sites in Rec8 promoting cleavage. We found that Rec8 cleavage depends on Aurora B/C kinase activity, and identified an aminoacid residue that is phosphorylated in vivo. Accordingly, inhibition of Aurora B/C kinase during meiotic maturation impairs endogenous Rec8 phosphorylation and chromosome segregation.
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https://hal.archives-ouvertes.fr/hal-03637686
Contributor : Katja Wassmann Connect in order to contact the contributor
Submitted on : Monday, April 11, 2022 - 6:05:46 PM
Last modification on : Monday, May 30, 2022 - 10:52:02 AM

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Elvira Nikalayevich, Safia El Jailani, Aude Dupré, Damien Cladière, Yulia Gryaznova, et al.. Aurora B/C-dependent phosphorylation promotes Rec8 cleavage in mammalian oocytes. Current Biology, 2022, ⟨10.1016/j.cub.2022.03.041⟩. ⟨hal-03637686⟩

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