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Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice

Journal article
Authors Marcello Stanzione
Marek Baumann
Frantzeskos Papanikos
Ihsan Dereli
Julian Lange
Angelique Ramlal
Daniel Tränkner
Hiroki Shibuya
Bernard De Massy
Yoshinori Watanabe
Maria Jasin
Scott Keeney
Attila Tóth
Published in Nature Cell Biology
Volume 18
Pages 1208-1220
ISSN 1465-7392
Publication year 2016
Published at Department of Chemistry and Molecular Biology
Pages 1208-1220
Language en
Links dx.doi.org/10.1038/ncb3417
Subject categories Cell Biology

Abstract

© 2016 Macmillan Publishers Limited. part of Springer Nature All rights reserved. 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.

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