BRCA1 Is Associated with a Human SWI/SNF-Related Complex: Linking Chromatin Remodeling to Breast Cancer

• Published in: Cell 2000-07, Vol.102 (2), p.257-265
• Main Authors: Bochar, Daniel A, Wang, Lai, Beniya, Hideo, Kinev, Alexander, Xue, Yutong, Lane, William S, Wang, Weidong, Kashanchi, Fatah, Shiekhattar, Ramin
• Format: Article
• Language: English
• Subjects: BRCA1 Protein - isolation & purification; BRCA1 Protein - metabolism; Breast Neoplasms - metabolism; Chromatin - metabolism; Chromatography, Affinity - methods; Chromosomal Proteins, Non-Histone; DNA Helicases; DNA-Binding Proteins - metabolism; Female; HeLa Cells; Humans; Nuclear Proteins - metabolism; SMARCB1 Protein; Transcription Factors - metabolism; Transcriptional Activation
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)00030-1

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.