Tumor suppressor p53 is required to modulate BRCA1 expression

Individuals carrying mutations in BRCA1 or p53 genes are predisposed to a v ariety of cancers, and both tumor suppressor genes have been implicated in DNA damage response pathways. We have analyzed a possible functional link b etween p53 and BRCA1 genes. Here we show that BRCA1 expression levels are d own-regulated in response to p53 induction in cells that undergo either gro wth arrest, senescence, or apoptosis. Physiological stimuli, such as exposu re to DNA-damaging agents, also result in negative regulation of BRCA1 leve ls in a p53-dependent manner prior to causing cell cycle arrest. Nuclear ru n-on experiments and luciferase reporter assays demonstrate that the change s in BRCA1 expression are mainly due to transcriptional repression induced by p53. In conclusion, the data show that BRCA1 expression levels are contr olled by the presence and activity of wild-type p53 and suggest the existen ce of an intracellular p53/BRCA1 pathway in the response of cells to stress conditions.