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


Authors: Stanzione, M.; Baumann, M.; Papanikos, F.; Dereli, I.; Lange, J.; Ramlal, A.; Trankner, D.; Shibuya, H.; de Massy, B.; Watanabe, Y.; Jasin, M.; Keeney, S.; Toth, A.
Article 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.
Keywords: mouse; synapsis; double-strand breaks; recombination; saccharomyces-cerevisiae; mammalian meiosis; schizosaccharomyces-pombe; prophase arrest; inactivation; spo11; hormad1
Journal Title: Nature Cell Biology
Volume: 18
Issue: 11
ISSN: 1465-7392
Publisher: Nature Publishing Group  
Date Published: 2016-11-01
Start Page: 1208
End Page: 1220
Language: English
ACCESSION: WOS:000387165600014
DOI: 10.1038/ncb3417
PROVIDER: wos
PMCID: PMC5089853
PUBMED: 27723721
Notes: Article -- Source: Wos
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MSK Authors
  1. Scott N Keeney
    111 Keeney
  2. Julian Lange
    16 Lange
  3. Maria Jasin
    223 Jasin