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.
Bochar
D A
DA
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Wang
L
L
Beniya
H
H
Kinev
A
A
Xue
Y
Y
Lane
W S
WS
Wang
W
W
Kashanchi
F
F
Shiekhattar
R
R
D019313:BRCA1 Protein / Q000302:isolation & purification / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D002846:Chromatography, Affinity / Q000379:methods; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D019313:BRCA1 Protein; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C101681:SMARCC1 protein, human; C101682:SMARCC2 protein, human; C109786:SMARCD1 protein, human; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases