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

Ihsan Dereli, Vladyslav Telychko, Frantzeskos Papanikos, Kavya Raveendran, Jiaqi Xu, Michiel Boekhout, Marcello Stanzione, Benjamin Neuditschko, Naga Sailaja Imjeti, Elizaveta Selezneva, Hasibe Tuncay, Sevgican Demir, Teresa Giannattasio, Marc Gentzel, Anastasiia Bondarieva, Michelle Stevense, Marco Barchi, Arp Schnittger, John R Weir, Franz HerzogScott Keeney, Attila Tóth

Research output: Contribution to journalArticlepeer-review

Abstract

Programmed DNA double-strand break (DSB) formation is a unique meiotic feature that initiates recombination-mediated linking of homologous chromosomes, thereby enabling chromosome number halving in meiosis. DSBs are generated on chromosome axes by heterooligomeric focal clusters of DSB-factors. Whereas DNA-driven protein condensation is thought to assemble the DSB-machinery, its targeting to chromosome axes is poorly understood. We discovered in mice that efficient biogenesis of DSB-machinery clusters requires seeding by axial IHO1 platforms, which are based on a DBF4-dependent kinase (DDK)-modulated interaction between IHO1 and the chromosomal axis component HORMAD1. IHO1-HORMAD1-mediated seeding of the DSB-machinery on axes ensures sufficiency of DSBs for efficient pairing of homologous chromosomes. Without IHO1-HORMAD1 interaction, residual DSBs depend on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, recombination initiation is ensured by complementary pathways that differentially support seeding and growth of DSB-machinery clusters, thereby synergistically enabling DSB-machinery condensation on chromosomal axes.

Original languageEnglish
Article number2941
Pages (from-to)2941
JournalNature Communications
Volume15
Issue number1
DOIs
Publication statusPublished - 27 Nov 2023

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