Insights into the functions of BRCA1 and BRCA2.

Since BRCA1 and BRCA2 were cloned five years ago, unraveling their normal functions has posed fascinating problems for cancer biologists. Both genes are novel, and little of their normal function was revealed by their sequence. Both genes contribute to homologous recombination and DNA repair, to embryonic proliferation, to transcriptional regulation and, for BRCA1, to ubiquitination. But questions regarding BRCA1 and BRCA2 biology remain, and their resolution is critical for clinical development. Why do ubiquitously expressed genes that participate in universal pathways lead, when mutant, specifically to breast and ovarian cancer? Why are the same genes required for embryonic proliferation and for tumor suppression?