1. SUMO fosters assembly and functionality of the MutSγ complex to facilitate meiotic crossing over.
- Author
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He W, Verhees GF, Bhagwat N, Yang Y, Kulkarni DS, Lombardo Z, Lahiri S, Roy P, Zhuo J, Dang B, Snyder A, Shastry S, Moezpoor M, Alocozy L, Lee KG, Painter D, Mukerji I, and Hunter N
- Subjects
- Cell Nucleus genetics, Chromosome Segregation, DNA genetics, DNA Damage, DNA Repair, DNA-Binding Proteins genetics, Saccharomyces cerevisiae growth & development, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Small Ubiquitin-Related Modifier Proteins genetics, Ubiquitin-Conjugating Enzymes genetics, Ubiquitin-Conjugating Enzymes metabolism, Crossing Over, Genetic, DNA-Binding Proteins metabolism, Meiosis, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae Proteins metabolism, Small Ubiquitin-Related Modifier Proteins metabolism, Sumoylation
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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