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

Autor: D A, Bochar, L, Wang, H, Beniya, A, Kinev, Y, Xue, W S, Lane, W, Wang, F, Kashanchi, R, Shiekhattar
Rok vydání: 2000
Předmět:
Zdroj: Cell. 102(2)
ISSN: 0092-8674
Popis: 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.
Databáze: OpenAIRE