BRCA1 PROTEIN IS LINKED TO THE RNA-POLYMERASE-II HOLOENZYME COMPLEX VIA RNA HELICASE A

The breast cancer specific tumour suppressor protein, BRCA1 (refs 1,2) , activates transcription when linked with a DNA-binding domain(3,4) a nd is a component of the RNA polymerase II (Pol II) holoenzyme(5,6). W e show here that RNA helicase A (RHA) protein(7,8) links BRCA1 to the holoenzyme complex. The region of BRCA1 which interacts with RHA and, thus, the holoenzyme complex, corresponds to subregions of the BRCT do main of BRCA1 (ref. 9). This interaction was shown to occur in yeast n uclei, and expression in human cells of a truncated RHA molecule which retains binding to BRCA1 inhibited transcriptional activation mediate d by the BRCA1 carboxy terminus. These data are the first to identify a specific protein interaction with the BRCA1 C-terminal domain and ar e consistent with the model that BRCA1 functions as a transcriptional coactivator.