A meiosis-specific BRCA2 binding protein recruits recombinases to DNA double-strand breaks to ensure homologous recombination

Nat Commun. 2019 Feb 13;10(1):722. doi: 10.1038/s41467-019-08676-2.


Homologous recombination (HR) repairs DNA double-strand breaks (DSBs) to maintain genomic integrity. Recombinase recruited to the DSBs by the mediator protein BRCA2 catalyzes the homology-directed repair. During meiotic HR, programmed DSBs are introduced genome-wide but their repair mechanisms, including the regulation of BRCA2, have remained largely elusive. Here we identify a meiotic localizer of BRCA2, MEILB2/HSF2BP, that localizes to the site of meiotic DSBs in mice. Disruption of Meilb2 abolishes the localization of RAD51 and DMC1 recombinases in spermatocytes, leading to errors in DSB repair and male sterility. MEILB2 directly binds to BRCA2 and regulates its association to meiotic DSBs. We map the MEILB2-binding domain within BRCA2 that is distinct from the canonical DNA-binding domain but is sufficient to localize to meiotic DSBs in a MEILB2-dependent manner. We conclude that localization of BRCA2 to meiotic DSBs is mediated by MEILB2, which is an integral mechanism to repair abundant meiotic DSBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA2 Protein / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Repair
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Knockout Techniques
  • Homologous Recombination*
  • Male
  • Meiosis / physiology*
  • Mice
  • Nuclear Proteins / metabolism
  • Phosphate-Binding Proteins
  • Rad51 Recombinase / metabolism
  • Recombinases / metabolism*


  • BRCA2 Protein
  • BRCA2 protein, mouse
  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Dmc1 protein, mouse
  • Nuclear Proteins
  • Phosphate-Binding Proteins
  • Recombinases
  • Rad51 Recombinase