ANKRD31 anchors meiotic double-strand break formation as a direct partner of REC114
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ABSTRACT: Homologous recombination initiated by double-strand breaks (DSBs) is crucial for chromosome pairing and segregation during meiosis. Here we unveil mouse ANKRD31 as a lynchpin controlling DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to X and Y pseudoautosomal regions (PAR). They also have delayed and fewer recombination sites but, paradoxically, more total DSBs, indicating DSB dysregulation. Unrepaired DSBs and pairing failures—stochastic on autosomes, nearly absolute on X and Y—cause meiotic arrest and male sterility, while Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines direct ANKRD31–REC114 molecular contacts and reveals a surprising pleckstrin homology domain in REC114. In vivo, ANKRD31 recruits REC114 to the PAR and elsewhere. Our findings inform a model that ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, promoting efficient and timely DSB formation but also suppressing formation of clustered DSBs.
ORGANISM(S): Mus musculus
PROVIDER: GSE118913 | GEO | 2019/12/25
REPOSITORIES: GEO
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