title: Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice.
abstract: DNA double-strand breaks (DSBs) are induced by SPO11 during meiosis to initiate recombination-mediated pairing and synapsis of homologous chromosomes. Germline genome integrity requires spatiotemporal control of DSB formation, which involves the proteinaceous chromosome axis along the core of each meiotic chromosome. In particular, a component of unsynapsed axes, HORMAD1, promotes DSB formation in unsynapsed regions where DSB formation must occur to ensure completion of synapsis. Despite its importance, the underlying mechanism has remained elusive. We identify CCDC36 as a direct interactor of HORMAD1 (IHO1) that is essential for DSB formation. Underpinning this function, IHO1 and conserved SPO11-auxiliary proteins MEI4 and REC114 assemble chromatin-bound recombinosomes that are predicted activators of DSB formation. HORMAD1 is needed for robust recruitment of IHO1 to unsynapsed axes and efficient formation and/or stabilization of these recombinosomes. Thus, we propose that HORMAD1-IHO1 interaction provides a mechanism for the selective promotion of DSB formation along unsynapsed chromosome axes.
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Marcello
authors.initials: M
authors.lastname: Stanzione
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Frantzeskos
authors.initials: F
authors.lastname: Papanikos
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Ihsan
authors.initials: I
authors.lastname: Dereli
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Lange
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Angelique
authors.initials: A
authors.lastname: Ramlal
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tränkner
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo 113-0032, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibuya
authors.affiliation: Institute of Human Genetics, UPR 1142, CNRS, University of Montpellier, 141, rue de la Cardonille, 34396 Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: de Massy
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo 113-0032, Japan.
authors.forename: Yoshinori
authors.identifier: http://orcid.org/0000-0002-5488-4812
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jasin
authors.affiliation: Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.|Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Scott
authors.identifier: http://orcid.org/0000-0002-1283-6417
authors.initials: S
authors.lastname: Keeney
authors.affiliation: Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Tóth
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000378:metabolism; D008540:Meiosis; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D013573:Synaptonemal Complex / Q000235:genetics / Q000378:metabolism*; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004706:Endodeoxyribonucleases; D009687:Nuclear Proteins; D000099257:Meiotic Recombination Protein SPO11; C506693:Nohma protein, mouse