Journal
NATURE CELL BIOLOGY
Volume 18, Issue 11, Pages 1208-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3417
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Funding
- DIGS-BB programme
- Deutsche Forschungsgemeinschaft (DFG) [TO421/3-2, SPP1384: TO421/4-2, TO421/51, TO421/6-1, TO421/8-1, TO421/8-2]
- JSPS
- European Research Council Executive Agency under the European Community's Seventh Framework Programme (FP7) [322788]
- NIH [R01 GM105421]
- American Cancer Society [PF-12-157-01-DMC]
- Grants-in-Aid for Scientific Research [25000014] Funding Source: KAKEN
- European Research Council (ERC) [322788] Funding Source: European Research Council (ERC)
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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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