Nine novel conserved motifs in BRCA1 identified by the chicken orthologue

Abstract

The breast cancer susceptibility gene BRCA1 encodes a multifunctional protein that is mutated in many hereditary breast and ovarian cancers. We have cloned a homologue of the human BRCA1 gene from chicken; the gene encodes a 1749 amino acid protein that is 33% identical to human BRCA1. Phylogenetic analyses of the chicken and mammalian proteins indicate that the chicken gene is a bona fide BRCA1 orthologue, the first to be described from a non-mammal. Most of the chicken protein has diverged considerably from its mammalian orthologues, although the RING and BRCT repeat regions are highly conserved. This marked overall sequence divergence has allowed us to identify nine additional highly-conserved motifs (ranging from 8--56 amino acids in length) which are likely important for BRCA1 function.