BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer.
Germline mutations in the tumor suppressor gene, BRCA1, predispose individuals to breast and ovarian cancers. Using a combination of affinity- and conventional chromatographic techniques, we have isolated a predominant form of a multiprotein BRCA1-containing complex from human cells displaying chromatin-remodeling activity. Mass spectrometric sequencing of components of this complex indicated that BRCA1 is associated with a SWI/SNF-related complex. We show that BRCA1 can directly interact with the BRG1 subunit of the SWI/SNF complex. Moreover, p53-mediated stimulation of transcription by BRCA1 was completely abrogated by either a dominant-negative mutant of BRG1 or the cancer-causing deletion in exon 11 of BRCA1. These findings reveal a direct function for BRCA1 in transcriptional control through modulation of chromatin structure.
Pubmed ID: 10943845 RIS Download
BRCA1 Protein | Breast Neoplasms | Chromatin | Chromatography, Affinity | Chromosomal Proteins, Non-Histone | DNA Helicases | DNA-Binding Proteins | Female | HeLa Cells | Humans | Nuclear Proteins | SMARCB1 Protein | Transcription Factors | Transcriptional Activation