Identification of a RING protein that can interact in vivo with the BRCA1 gene product

The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine–rich RING motif, a zinc–binding domain found in a variety of regulatory proteins. Here we describe a novel protein that interacts in vivo with the N–terminal region of BRCA1. This BRCA1–associated RING domain (BARD1) protein contains an N–terminal RING motif, three tandem ankyrin repeats, and a C–terminal sequence with significant homology to the phylogenetically conserved BRCT domains that lie near the C terminus of BRCA1. The BARD1/BRCA1 interaction is disrupted by BRCA1 missense mutations that segregate with breast cancer susceptibility, indicating that BARD1 may be involved in mediating tumour suppression by BRCA1.