Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice

Abstract : In most taxa, halving of chromosome numbers during meiosis requires that homologous chromosomes (homologues) pair and form crossovers. Crossovers emerge from the recombination-mediated repair of programmed DNA double-strand breaks (DSBs). DSBs are generated by SPO11, whose activity requires auxiliary protein complexes, called pre-DSB recombinosomes. To elucidate the spatiotemporal control of the DSB machinery, we focused on an essential SPO11 auxiliary protein, IHO1, which serves as the main anchor for pre-DSB recombinosomes on chromosome cores, called axes. We discovered that DSBs restrict the DSB machinery by at least four distinct pathways in mice. Firstly, by activating the DNA damage response (DDR) kinase ATM, DSBs restrict pre-DSB recombinosome numbers without affecting IHO1. Secondly, in their vicinity, DSBs trigger IHO1 depletion mainly by another DDR kinase, ATR. Thirdly, DSBs enable homologue synapsis, which promotes the depletion of IHO1 and pre-DSB recombinosomes from synapsed axes. Finally, DSBs and three DDR kinases, ATM, ATR and PRKDC, enable stage-specific depletion of IHO1 from all axes. We hypothesize that these four negative feedback pathways protect genome integrity by ensuring that DSBs form without excess, are well-distributed, and are restricted to genomic locations and prophase stages where DSBs are functional for promoting homologue pairing and crossover formation.
Liste complète des métadonnées

https://hal.umontpellier.fr/hal-03433922
Contributeur : Bernard de Massy Connectez-vous pour contacter le contributeur
Soumis le : jeudi 18 novembre 2021 - 08:32:00
Dernière modification le : vendredi 5 août 2022 - 10:32:59
Archivage à long terme le : : samedi 19 février 2022 - 18:18:07

Fichier

Dereli-2021-Four-pronged negat...
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Collections

Citation

Ihsan Dereli, Marcello Stanzione, Fabrizio Olmeda, Frantzeskos Papanikos, Marek Baumann, et al.. Four-pronged negative feedback of DSB machinery in meiotic DNA-break control in mice. Nucleic Acids Research, Oxford University Press, 2021, 49, pp.2609 - 2628. ⟨10.1093/nar/gkab082⟩. ⟨hal-03433922⟩

Partager

Métriques

Consultations de la notice

9

Téléchargements de fichiers

21