SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over

Area of Science:

• Genetics
• Molecular Biology
• Cell Biology

Background:

• Crossing over is crucial for accurate chromosome segregation during meiosis.
• SUMOylation (Small Ubiquitin-like Modifier) is a post-translational modification involved in various cellular processes, including DNA repair and chromosome dynamics.
• The precise targets of SUMOylation in regulating meiotic crossovers have been largely unidentified.

Purpose of the Study:

• To identify and characterize the role of SUMOylation in regulating meiotic crossover control.
• To investigate Msh4 as a direct target of SUMOylation in the context of crossover regulation.

Main Methods:

• Proteomic analysis to identify SUMOylation targets.
• Biochemical assays to study protein-protein interactions and enzyme activity.
• Analysis of DNA double-strand break responses and meiotic progression in yeast models.

Main Results:

• Msh4, a subunit of the MutSγ complex, is identified as a direct target of SUMOylation.
• SUMOylation of Msh4 enhances the stabilization of joint-molecule (JM) recombination intermediates and promotes crossover formation.
• Msh4 is SUMOylated by Ubc9 in response to DNA double-strand breaks, with distinct mono- and multi/poly-SUMOylated forms observed.
• SUMOylation promotes the interaction between Msh4 and Msh5, facilitating MutSγ complex function.

Conclusions:

• Msh4 SUMOylation is a critical regulatory mechanism for ensuring at least one crossover per chromosome pair during meiosis.
• SUMOylation of Msh4 acts independently of its phosphorylation, establishing MutSγ as a central hub for crossover control.
• This regulation is essential for accurate chromosome segregation and genomic stability.