BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer

Daniel A. Bochar, Lai Wang, Hideo Beniya, Alexander Kinev, Yutong Xue, William S. Lane, Weidong Wang, Fatah Kashanchi, Ramin Shiekhattar

Research output: Contribution to journalArticlepeer-review

425 Scopus citations

Abstract

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 ceils 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.

Original languageEnglish (US)
Pages (from-to)257-265
Number of pages9
JournalCell
Volume102
Issue number2
DOIs
StatePublished - Jul 21 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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