Most familial breast and ovarian cancers have been Linked to mutations in t
he BRCA1 gene. BRCA1 has been shown to affect gene transcription but how it
does so remains elusive. Here we show that BRCA1 can stimulate transcripti
on without the requirement for a DNA-tethering function in mammalian and ye
ast cells. Furthermore, the BRCA1 C-terminal region can stimulate transcrip
tion of the p53-responsive promoter, MDM2. Unlike many enhancer-specific ac
tivators, non-tethered BRCA1 does not require a functional TATA element to
stimulate transcription. Our results suggest that BRCA1 can enhance transcr
iption by a function additional to recruiting the transcriptional machinery
to a targeted gene.