BRCA1 regulation of transcription.

BRCA1, a tumor suppressor gene on chromosome 17q21, was identified in 1994 based on its linkage to hereditary breast and ovarian cancer syndromes. The BRCA1 gene encodes a 220 kDa nuclear phosphoprotein. Studies aimed at elucidating the mechanisms of its tumor suppressor activity have revealed, in part, that BRCA1 participates in the DNA damage response and acts to maintain the integrity of the genome. This activity is generic and does not account for the propensity of BRCA1 mutation carriers to develop specific tumor types rather than a broad spectrum of cancers. In addition to genome maintenance, BRCA1 has been found to broadly regulate gene transcription, even though it is not itself a sequence-specific DNA-binding transcription factor. The ability of BRCA1 to function as a coregulator of transcription may underlie some of its tumor suppressor activity and may explain the tissue-specific nature of this activity. This review will focus on how BRCA1 selectively regulates transcription and how this regulatory function may relate to tumor suppression.