The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells

Nat Commun. 2020 Apr 28;11(1):2055. doi: 10.1038/s41467-020-15954-x.


Breast cancer susceptibility gene II (BRCA2) is central in homologous recombination (HR). In meiosis, BRCA2 binds to MEILB2 to localize to DNA double-strand breaks (DSBs). Here, we identify BRCA2 and MEILB2-associating protein 1 (BRME1), which functions as a stabilizer of MEILB2 by binding to an α-helical N-terminus of MEILB2 and preventing MEILB2 self-association. BRCA2 binds to the C-terminus of MEILB2, resulting in the formation of the BRCA2-MEILB2-BRME1 ternary complex. In Brme1 knockout (Brme1-/-) mice, the BRCA2-MEILB2 complex is destabilized, leading to defects in DSB repair, homolog synapsis, and crossover formation. Persistent DSBs in Brme1-/- reactivate the somatic-like DNA-damage response, which repairs DSBs but cannot complement the crossover formation defects. Further, MEILB2-BRME1 is activated in many human cancers, and somatically expressed MEILB2-BRME1 impairs mitotic HR. Thus, the meiotic BRCA2 complex is central in meiotic HR, and its misregulation is implicated in cancer development.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • BRCA2 Protein / metabolism*
  • Cell Line, Tumor
  • Chromosome Pairing
  • DNA Breaks, Double-Stranded
  • Homologous Recombination / genetics*
  • Male
  • Meiosis / genetics*
  • Mice, Inbred C57BL
  • Mitosis / genetics*
  • Multiprotein Complexes / metabolism*
  • Neoplasms / genetics*
  • Protein Binding
  • Protein Stability
  • Rad51 Recombinase / metabolism*
  • Spermatozoa / metabolism


  • BRCA2 Protein
  • Multiprotein Complexes
  • Rad51 Recombinase