BRCA2 ASSOCIATES WITH ACETYLTRANSFERASE ACTIVITY WHEN BOUND TO P CAF/

Predisposition to hereditary breast cancer has been attributed in part to inherited mutations in the BRCA2 gene. The large protein it encode s is still poorly characterized with respect to functions. We have pre viously shown that BRCA2 has transcriptional activation potential conf erred by its amino-terminal third exon, Here, me show that BRCA2 inter acts with a transcriptional co-activator protein, P/CAF, which possess es histone acetyltransferase activity, The interaction with P/CAF is d emonstrated in vitro as well as in vivo and is shown to be mediated by residues 290-453 of BRCA2, Consistent with the binding to an acetyltr ansferase, BRCA2 is shown to associate with acetyltransferase activity in nuclear extracts. Contrary to a recent report, we find no evidence in support of an intrinsic HAT activity in BRCA2 amino-terminus. Our results further substantiate the notion that BRCA2 has transcriptional activation function and suggest that one mechanism by which BRCA2 reg ulates transcription may be through the recruitment of histone-modifyi ng activity of the P/CAF co-activator.