Breast cancer type 1 susceptibility protein-BRCA1-associated RING domain protein 1 heterodimer (BRCA1-BARD1) (BRCA1-BARD1)

The Breast cancer type 1 susceptibility protein-BRCA1-associated RING domain protein 1 (BRCA1-BARD1) heterodimer is a critical E3 ubiquitin ligase complex essential for maintaining genomic integrity (UniProt P38398; UniProt Q99728). The interaction between the N-terminal RING domains of BRCA1 and BARD1 is necessary for the metabolic stability of BRCA1 and significantly enhances its enzymatic activity, which is vital for DNA double-strand break repair through homologous recombination (PubMed: 11323670). Beyond DNA repair, the complex plays roles in cell cycle checkpoint regulation and the maintenance of centrosome stability (PubMed: 28241148). Mutations that disrupt the formation or function of this heterodimer are strongly associated with an increased risk of hereditary breast, ovarian, and other cancers (National Cancer Institute). While the complex itself is not typically the direct target of small molecule inhibitors, its functional absence or impairment is the basis for synthetic lethality strategies using PARP inhibitors, such as Olaparib and Niraparib, which selectively kill cells lacking functional homologous recombination (PubMed: 15832242). Therapeutic challenges include the development of resistance, often through secondary reversion mutations that restore the complex's function.

Other names

BRCA1-BARD1 complexBRCA1/BARD1 E3 ubiquitin ligaseRNF53-BARD1 complexBreast cancer 1-BRCA1 associated RING domain 1 heterodimer

Synthetic lethality through PARP inhibition in cells with deficient BRCA1-BARD1 mediated homologous recombination repair