Insights into the functions of BRCA1 and BRCA2

Since BRCA1 and BRCA2 were cloned five years ago, unraveling their normal f unctions has posed fascinating problems for cancer biologists. Bath genes a re novel, and little of their normal function was revealed by their sequenc e. Both genes contribute to homologous recombination and DNA repair, to emb ryonic proliferation, to transcriptional regulation and, for BRCA1, to ubiq uitination. But questions regarding BRCA1 and BRCA2 biology remain, and the ir resolution is critical for clinical development. Why do ubiquitously exp ressed genes that participate in universal pathways lead, when mutant, spec ifically to breast and ovarian cancer? Why are the same genes required for embryonic proliferation and for tumor suppression?