The BRCA1 tumor suppressor gene is expressed in all mammalian cells. Within 
these cells, the BRCA1 protein product interacts with several seemingly distinct 
nuclear complexes. Proteins within these complexes are potential targets for the 
E3-ubiquitin ligase activity associated with BRCA1:BARD1 complexes. Recent 
breakthroughs have centered on elucidating critical DNA repair and 
chromatin-remodeling functions associated with BRCA1 activity. During both DNA 
replication and DNA repair, BRCA1 appears to serve both adaptor and enzymatic 
functions. Roles include transient physical recruitment of NBS1, gammaH2AX, 
FANCD2 and other proteins in specific repair associated complexes, and enzymatic 
activity as an E3-ubiquitin ligase against a subset of these proteins. BRCA1 has 
also been implicated as a regulator of transcription. It is in this second 
capacity that progress has been much more difficult to assess. In particular, 
unambiguous adaptor and enzymatic functions have yet to be demonstrated in 
transcriptional machinery. Addressing the critical gap in our understanding of 
enzymatic targets of BRCA1 will be required for significant future progress in 
this field. The following review puts forward a model for BRCA1 interactions 
with the transcriptional complex in undamaged cells, and a potential mechanism 
for substrate switching between transcription and DNA-repair complexes following 
exposure of cells to proliferative or genotoxic stress. This model incorporates 
recent evidence that BRCA1 interacts predominantly with hyper-phosphorylated, 
enzymatically active, RNA polymerase II (RNAPII) in undamaged cells. The model 
proposes that BRCA1 binds processive RNA polymerase as part of a genome 
surveillance function, upstream of critical roles in DNA repair.