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. Epub 2016 Oct 10.


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.

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromatin / genetics
  • DNA Breaks, Double-Stranded*
  • DNA Replication / genetics
  • Endodeoxyribonucleases / metabolism
  • Meiosis
  • Mice, Knockout
  • Nuclear Proteins / metabolism
  • Recombination, Genetic / genetics
  • Synaptonemal Complex / genetics
  • Synaptonemal Complex / metabolism*


  • Cell Cycle Proteins
  • Chromatin
  • Nohma protein, mouse
  • Nuclear Proteins
  • Endodeoxyribonucleases
  • meiotic recombination protein SPO11