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 chrom...

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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
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container_issue 2
container_start_page 257
container_title Cell
container_volume 102
creator Bochar, Daniel A
Wang, Lai
Beniya, Hideo
Kinev, Alexander
Xue, Yutong
Lane, William S
Wang, Weidong
Kashanchi, Fatah
Shiekhattar, Ramin
description 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.
doi_str_mv 10.1016/S0092-8674(00)00030-1
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source ScienceDirect Journals
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
title BRCA1 Is Associated with a Human SWI/SNF-Related Complex: Linking Chromatin Remodeling to Breast Cancer
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