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:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85066436283&doi=10.1016%2fj.molcel.2019.03.023&partnerID=40&md5=0e387a828f214d48fcfec47abdb1b6e2
Notes:	Source: Scopus