BARD1 participates with BRCA1 in homology-directed repair of chromosome breaks

Mol Cell Biol. 2003 Nov;23(21):7926-36. doi: 10.1128/MCB.23.21.7926-7936.2003.


The BRCA1 tumor suppressor has been implicated in the maintenance of chromosomal stability through homology-directed repair of DNA double-strand breaks. Much of the BRCA1 in cells forms a heterodimeric complex with a structurally related protein BARD1. We report that expression of truncated mouse or human BARD1 peptides capable of interacting with Brca1 results in a homologous-repair deficiency. Repair is mildly reduced in Brca1 wild-type cells and severely reduced in cells that harbor a Brca1 splice product deleted for exon 11. Nuclear localization of the Brca1 or BARD1 peptides is not compromised, implying that the repair deficiency is caused by a more direct effect on repair. The tumor suppressor activity of BRCA1 may require the participation of BARD1 to maintain chromosome integrity through the homologous-repair pathway.

Publication types

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

MeSH terms

  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chromosomes / metabolism*
  • DNA Damage
  • DNA Repair
  • Genes, Reporter
  • Humans
  • Macromolecular Substances
  • Mice
  • Mice, Knockout
  • Mitomycin / metabolism
  • Nucleic Acid Synthesis Inhibitors / metabolism
  • Peptides / genetics
  • Peptides / metabolism
  • Protein Binding
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*


  • BRCA1 Protein
  • Carrier Proteins
  • Macromolecular Substances
  • Nucleic Acid Synthesis Inhibitors
  • Peptides
  • Tumor Suppressor Proteins
  • Mitomycin
  • BARD1 protein, human
  • Bard1 protein, mouse
  • Ubiquitin-Protein Ligases