Sequence analysis of the rat Brca1 homolog and its promoter region

Since the identification of the human breast and ovarian cancer gene, BRCA1 , a large spectrum of germline mutations has been characterized that predis pose women to developing these diseases. We have determined the complete co ding sequence for the rat BRCA1 homolog and compared it with those of the m ouse, dog, and human to help identify the important functional domains of t he BRCA1 protein. The overall rat Brcal amino acid identity compared with t he predicted mouse, dog, and human gene products is 81%, 69%, and 58%, resp ectively. In spite of this low overall homology, the amino terminal RING fi nger domain and one of two nuclear localization signals are highly conserve d among these species. In addition, two BRCT domains at the carboxy terminu s and a highly acidic region are relatively well conserved. We have also id entified several putative regulatory elements through comparison of the bid irectional BRCA1 promoter regions among the rat, mouse, and human genes. Th ese include motifs for CCAAT and GIC boxes, as well as potential SP1, CREB, and NFkB transcription factor binding sites. Finally, analysis of splice v ariants from rat mammary gland, ovary, testis, spleen, and liver tissues re vealed that, while alternative transcripts are detectable, full-length tran scripts are the predominant steady-state form.