Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes

• DOI: 10.1038/s41467-024-47020-1
• Publication Date: 2024-04-05T09:02:06Z
• Authors: Ihsan Dereli; Vladyslav Telychko; Frantzeskos Papan...; Kavya Raveendran; Jiaqi Xu; Michiel Boekhout; Marcello Stanzione; Benjamin Neuditschko; Naga Sailaja Imjeti; Elizaveta Selezneva; Hasibe Tuncay; Sevgican Demir; Teresa Giannattasio; Marc Gentzel; Anastasiia Bondar...; Michelle Stevense; Marco Barchi; Arp Schnittger; John R. Weir; Franz Herzog; Scott Keeney; Attila Tóth
• Keywords: Recombination, Genetic; Settore BIO/16; 570; Synaptonemal Complex; Science; Q; 500; Cell Cycle Proteins; DNA; Article; Mice; Meiosis; Animals; DNA Breaks, Double-Stranded; Homologous Recombination

Abstract Programmed DNA double-strand break (DSB) formation is a crucial feature of meiosis in most organisms. DSBs initiate recombination-mediated linking homologous chromosomes, which enables correct chromosome segregation meiosis. are generated on axes by heterooligomeric focal clusters DSB-factors. Whereas DNA-driven protein condensation thought to assemble the DSB-machinery, its targeting poorly understood. We uncover mice that efficient biogenesis DSB-machinery requires seeding axial IHO1 platforms. Both phosphorylation and platforms diminished chemical inhibition DBF4-dependent kinase (DDK), suggesting DDK contributes control DSB-machinery. Furthermore, we show based an interaction between chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated ensures sufficiency for pairing chromosomes. Without IHO1-HORMAD1 interaction, residual depend ANKRD31, enhances both growth clusters. Thus, recombination initiation ensured complementary pathways differentially support clusters, thereby synergistically enabling axes.