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Bernard DE MASSY, 'Institut de Génétique Humaine (IGH) - Montpellier

Programmed DNA double-strand breaks during meiosis: Mechanism and evolution
Quand ? Le 28/11/2025,
de 11:00 à 12:00
S'adresser à Equipe PIAZZA, Salle des Thèses
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Meiotic cells have developed a sophisticated molecular pathway allowing homologous chromosome to pair, be connected and exchanged. This pathway relies on homologous recombination events which are initiated by the programmed induction of DNA double strands breaks (DSBs). The absence of meiotic recombination leads to sterility. In mammals, about 300 DSBs are induced in each oocyte or spermatocyte at the onset of the first meiotic prophase.

We discovered several years ago that the distribution of meiotic recombination is determined by PRDM9 in humans and mice. PRDM9 is a sequence-specific DNA binding protein with a methyl-transferase activity, catalysing H3K4me3 and H3K36me3. We also identified the long-sought missing subunit for DNA break formation, TOPOVIBL, a partner of SPO11 carrying the catalytic activity, and also highlighting the evolutionary link with Type II DNA Topoisomerases. I will present our current view of how PRDM9 mediates its function at the DNA level and in the context of chromosome organisation, and report recent insights into its evolutionary conservation.

 

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