REC114 Partner ANKRD31 Controls Number, Timing, and Location of Meiotic DNA Breaks

Mol Cell. 2019 Jun 6;74(5):1053-1068.e8. doi: 10.1016/j.molcel.2019.03.023. Epub 2019 Apr 16.


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.

Keywords: Ankrd31; DNA double-strand break; Prdm9; Spo11; homologous recombination; meiosis; oogenesis; premature ovarian failure; pseudoautosomal region; spermatogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Chromosome Pairing
  • Chromosome Segregation / genetics
  • Chromosomes
  • Crystallography, X-Ray
  • DNA Breaks, Double-Stranded
  • Female
  • Homologous Recombination / genetics*
  • Male
  • Meiosis / genetics*
  • Mice
  • Protein Conformation
  • Recombinases / chemistry*
  • Recombinases / genetics
  • Spermatocytes / chemistry
  • Spermatocytes / metabolism


  • Ankrd31 protein, mouse
  • Cell Cycle Proteins
  • Rec114 protein, mouse
  • Recombinases