2. Academic Validation
  3. Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice

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

  • Nat Cell Biol. 2016 Nov;18(11):1208-1220. doi: 10.1038/ncb3417.
Marcello Stanzione 1,  Marek Baumann 1,  Frantzeskos Papanikos 1,  Ihsan Dereli 1,  Julian Lange 2,  Angelique Ramlal 1,  Daniel Tränkner 1,  Hiroki Shibuya 3,  Bernard de Massy 4,  Yoshinori Watanabe 3,  Maria Jasin 5,  Scott Keeney 2 6,  Attila Tóth 1
Affiliations

Affiliations

  • 1 Institute of Physiological Chemistry, Faculty of Medicine at the TU Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
  • 2 Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • 3 Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi 1-1-1, Tokyo 113-0032, Japan.
  • 4 Institute of Human Genetics, UPR 1142, CNRS, University of Montpellier, 141, rue de la Cardonille, 34396 Montpellier, France.
  • 5 Developmental Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
  • 6 Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
PMID: 27723721 DOI: 10.1038/ncb3417
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.

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