The breast- and ovarian-specific tumor suppressor, BRCA1, has been implicated to 
function in many nuclear processes, including DNA damage repair, recombination, 
transcription, ubiquitination, cell cycle checkpoint enforcement, and centrosome 
regulation. Utilizing a previously described interaction between BRCA1 and RNA 
helicase A (RHA), we have developed a dominant-negative approach to block BRCA1 
function in human breast epithelial cells. Overexpression of a truncated RHA 
peptide that can bind to the BRCA1 carboxy-terminus prevents normal BRCA1 
function, such as BRCA1 association with nuclear foci following DNA damage. 
Overexpression of this dominant-negative protein induces pleomorphic nuclei, 
aberrant mitoses with extra centrosomes, and tetraploidy. This model system 
allows us to observe changes to mammary epithelial cells that occur acutely 
following loss of BRCA1 function. Furthermore, inhibition of BRCA1 via 
overexpressing the RHA fragment coincides with a reduction in PARP-1 protein 
expression, suggesting a possible mechanism for BRCA1 in the maintenance of 
genomic integrity.