BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer
BRCA1 is associated with a human SWI/SNF-related complex: Linking chromatin remodeling to breast cancer
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DOI：
10.1016/s0092-8674(00)00030-1
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发表时间：
2000-07-21
期刊：
影响因子：
64.5
通讯作者：
Shiekhattar, R
中科院分区：
文献类型：
--
作者：
Bochar, DA;Wang, L;Shiekhattar, R
肿瘤抑制基因BRCA 1的生殖系突变使个体易患乳腺癌和卵巢癌。使用亲和和传统的色谱技术相结合，我们已经分离出一个主要形式的多蛋白BRCA 1含有复杂的人类细胞显示染色质重塑活性。该复合物的组分的质谱测序表明BRCA 1与SWI/SNF相关复合物相关。我们发现BRCA 1可以直接与SWI/SNF复合物的BRG 1亚基相互作用。此外，p53介导的BRCA 1转录刺激被BRG 1的显性负突变体或BRCA 1外显子11中的致癌缺失完全废除。这些发现揭示了BRCA 1通过调节染色质结构在转录控制中的直接功能。
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.