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

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Cohesin removal is crucial for generating haploid gametes during meiosis.
• Meiotic cohesin subunit Rec8 cleavage by separase is essential for chromosome and chromatid segregation.
• While Rec8 phosphorylation regulates cleavage in model organisms, its role in mammalian meiosis remains unclear.

Purpose of the Study:

• To investigate whether Rec8 cleavage in mammalian meiosis requires phosphorylation.
• To identify the specific kinases responsible for Rec8 phosphorylation and cleavage.
• To understand the functional significance of Rec8 phosphorylation in mammalian oocyte maturation.

Main Methods:

• Adapted a biosensor to detect separase activity in single mouse oocytes.
• Utilized live imaging to monitor Rec8 cleavage dynamics.
• Performed phosphomutant analysis to identify critical phosphorylation sites on Rec8.

Main Results:

• Demonstrated that Rec8 cleavage in mouse oocytes is dependent on phosphorylation.
• Identified Aurora B/C kinases as crucial for Rec8 phosphorylation.
• Pinpointed a specific amino acid residue phosphorylated in vivo, crucial for Rec8 cleavage.
• Showed that inhibiting Aurora B/C kinases impairs Rec8 phosphorylation and chromosome segregation.

Conclusions:

• Rec8 cleavage in mammalian meiosis is a regulated process dependent on phosphorylation.
• Aurora B/C kinases play a critical role in phosphorylating Rec8, facilitating its cleavage by separase.
• Understanding these mechanisms is vital for comprehending mammalian gametogenesis and potential reproductive disorders.