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.
Mesh Terms:
BRCA1 Protein, Breast Neoplasms, Chromatin, Chromatography, Affinity, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Female, Hela Cells, Humans, Nuclear Proteins, Transcription Factors, Transcriptional Activation
BRCA1 Protein, Breast Neoplasms, Chromatin, Chromatography, Affinity, Chromosomal Proteins, Non-Histone, DNA Helicases, DNA-Binding Proteins, Female, Hela Cells, Humans, Nuclear Proteins, Transcription Factors, Transcriptional Activation
Cell
Date: Jul. 21, 2000
PubMed ID: 10943845
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