THE BRC REPEATS ARE CONSERVED IN MAMMALIAN BRCA2 PROTEINS

The breast cancer susceptibility gene BRCA2 encodes a protein of 3418 amino acids which does not exhibit substantial sequence similarity to any other protein in the public databases. A dot matrix comparison of BRCA2 with itself revealed an eight times repeated motif in the segmen t of the protein encoded by exon 11. As a preliminary test of the hypo thesis that these motifs are functionally significant, we have sequenc ed exon 11 of BRCA2 in six mammals, An alignment of the predicted prot ein sequences shows that, overall, the motifs have been conserved whil e much of the intervening sequences has diverged. These data support t he notion that the BRC motifs are important in BRCA2 function, There i s, however, considerable interspecies variation within certain motif u nits, raising the possibility of redundancy and that not all of the re peats are required for the normal function of BRCA2.