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Molecular Interactions of Rec114-Mei4-Mer2 in the Control of Meiotic DNA Double-Strand Break Formation by Marita HADDAD -
Mercredi 1er avril 2026 à 16h00 - Salle Jean-Baptiste Carnoy (B.059) - Bâtiment Carnoy - Croix du Sud - 1348 Louvain-la-Neuve -
Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs), a process tightly regulated to ensure genome integrity and diversity. In Saccharomyces cerevisiae, the RMM complex (Rec114, Mei4, Mer2), together with other partners, orchestrates DSB formation. This thesis investigates the molecular mechanisms underlying this regulation, focusing on the organization, interactions, and functional dynamics of the RMM complex.
Using a combination of molecular genetics, proteomics, and genomic approaches, I first attempted to map the RMM interactome via TurboID proximity labeling, revealing methodological challenges in capturing transient meiotic interactions. I then explored the impact of RMM condensates on chromatin architecture using Hi-C, finding that artificial Hop1 tethering, rather than RMM proteins, dominated chromatin remodeling. Subsequent chapters uncovered a dual interaction interface between Hop1 and Mer2, demonstrating how modular contacts fine-tune DSB formation across the genome. Finally, I dissected the regulation of Mer2, showing how phosphorylation, structural flexibility, and competitive interactions coordinate its function.
Collectively, this work highlights the dynamic and multivalent nature of the DSB machinery, offering a framework for understanding how recombination initiation is integrated with chromosome structure and cell cycle.
Jury members :
Prof. Corentin CLAEYS BOUUAERT (UCLouvain) (Supervisor)
Prof. Bernard HALLET (UCLouvain) (Chairperson)
Prof. Pierre MORSOMME (UCLouvain) (Secretary)
Prof. Benoît DESGUIN (UCLouvain)
Prof. Valerie GARCIA (CRCM, Marseille, FR.)
Prof. Thomas ROBERT (CBS, Montpellier, FR.)
Pay attention : the public defense of Marita HADDAD will also take place in the form of a videoconference
