REC114 partner ANKRD31 controls number, timing, and location of meiotic DNA breaks Journal Article
| Authors: | Boekhout, M.; Karasu, M. E.; Wang, J.; Acquaviva, L.; Pratto, F.; Brick, K.; Eng, D. Y.; Xu, J.; Camerini-Otero, R. D.; Patel, D. J.; Keeney, S. |
| Article Title: | REC114 partner ANKRD31 controls number, timing, and location of meiotic DNA breaks |
| Abstract: | Double-strand breaks (DSBs) initiate the homologous recombination that is crucial for meiotic chromosome pairing and segregation. Here, we unveil mouse ANKRD31 as a lynchpin governing multiple aspects of DSB formation. Spermatocytes lacking ANKRD31 have altered DSB locations and fail to target DSBs to the pseudoautosomal regions (PARs) of sex chromosomes. They also have delayed and/or fewer recombination sites but, paradoxically, more DSBs, suggesting DSB dysregulation. Unrepaired DSBs and pairing failures—stochastic on autosomes, nearly absolute on X and Y—cause meiotic arrest and sterility in males. Ankrd31-deficient females have reduced oocyte reserves. A crystal structure defines a pleckstrin homology (PH) domain in REC114 and its direct intermolecular contacts with ANKRD31. In vivo, ANKRD31 stabilizes REC114 association with the PAR and elsewhere. Our findings inform a model in which ANKRD31 is a scaffold anchoring REC114 and other factors to specific genomic locations, thereby regulating DSB formation. Boekhout et al. discover ANKRD31 as a REC114 interactor and key player in meiotic recombination. ANKRD31 acts as a molecular scaffold to regulate double-strand break formation and promote X-Y recombination. An atomic resolution structure illuminates the conserved features of REC114-ANKRD31 interaction, including an unexpected pleckstrin homology domain in REC114. © 2019 Elsevier Inc. |
| Keywords: | meiosis; homologous recombination; spermatogenesis; oogenesis; spo11; premature ovarian failure; dna double-strand break; pseudoautosomal region; prdm9; ankrd31 |
| Journal Title: | Molecular Cell |
| Volume: | 74 |
| Issue: | 5 |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Date Published: | 2019-06-06 |
| Start Page: | 1053 |
| End Page: | 1068.e8 |
| Language: | English |
| DOI: | 10.1016/j.molcel.2019.03.023 |
| PUBMED: | 31003867 |
| PROVIDER: | scopus |
| PMCID: | PMC6555648 |
| DOI/URL: | |
| Notes: | Source: Scopus |
Altmetric
Citation Impact
Related MSK Work