1. SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over
- Author
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He, Wei, Verhees, Gerrik F, Bhagwat, Nikhil, Yang, Ye, Kulkarni, Dhananjaya S, Lombardo, Zane, Lahiri, Sudipta, Roy, Pritha, Zhuo, Jiaming, Dang, Brian, Snyder, Andriana, Shastry, Shashank, Moezpoor, Michael, Alocozy, Lilly, Lee, Kathy Gyehyun, Painter, Daniel, Mukerji, Ishita, and Hunter, Neil
- Subjects
double-strand break ,Saccharomyces cerevisiae Proteins ,DNA Repair ,1.1 Normal biological development and functioning ,MutS ,chromosome segregation ,crossing over ,DNA repair ,homologous recombination ,Saccharomyces cerevisiae ,Medical and Health Sciences ,protein modification ,Genetic ,Underpinning research ,Chromosome Segregation ,Crossing Over ,Genetics ,meiosis ,aneuploidy ,Cell Nucleus ,Sumoylation ,DNA ,Biological Sciences ,DNA-Binding Proteins ,Meiosis ,SUMO ,Ubiquitin-Conjugating Enzymes ,Small Ubiquitin-Related Modifier Proteins ,Generic health relevance ,DNA Damage ,Developmental Biology - Abstract
Crossing over is essential for chromosome segregation during meiosis. Protein modification by SUMO is implicated in crossover control, but pertinent targets have remained elusive. Here we identify Msh4 as a target of SUMO-mediated crossover regulation. Msh4 and Msh5 constitute the MutSγ complex, which stabilizes joint-molecule (JM) recombination intermediates and facilitates their resolution into crossovers. Msh4 SUMOylation enhances these processes to ensure that each chromosome pair acquires at least one crossover. Msh4 is directly targeted by E2 conjugase Ubc9, initially becoming mono-SUMOylated in response to DNA double-strand breaks, then multi/poly-SUMOylated forms arise as homologs fully engage. Mechanistically, SUMOylation fosters interaction between Msh4 and Msh5. We infer that initial SUMOylation of Msh4 enhances assembly of MutSγ in anticipation of JM formation, while secondary SUMOylation may promote downstream functions. Regulation of Msh4 by SUMO is distinct and independent of its previously described stabilization by phosphorylation, defining MutSγ as a hub for crossover control.
- Published
- 2021