The primary amino acid sequence of BRCA1 offers few clues about the mechanism by which it suppresses tumor formation in normal breast and ovarian tissues. In an effort to unravel its biological functions, investigators have sought to identify the proteins that interact with BRCA1 in vivo. These efforts have already uncovered two interacting proteins: the BRCA1-associated RING domain (BARD1) protein, a novel polypeptide that bears a striking structural resemblance to BRCA1, and hRAD51, a human homolog of the bacterial recA gene product. As proliferating cells enter S phase of the cell cycle, the BRCA1, hRAD51, and BARD1 polypeptides aggregate in discrete nuclear domains, commonly described as ``BRCA1 nuclear dots''. However, when S phase cells sustain DNA damage, the dots are mobilized such that BRCA1 and its associated proteins relocate to sites of replicating DNA. Thus, as a participant in the cellular response to DNA damage, BRCA1 may suppress tumor formation by preserving the integrity of genomic DNA.
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