BIOMEDICINE: Sniffing Out a Job for BRCA1

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Science  04 Aug 2000:
Vol. 289, Issue 5480, pp. 697e-699e
DOI: 10.1126/science.289.5480.697e

The discovery that mutations in the BRCA1 gene predispose individuals to an increased risk of developing breast or ovarian cancer has prompted the search for what the normal BRCA1 protein does in the cell. BRCA1 has structural motifs characteristic of transcription factors, and it increases the expression of certain genes including the master tumor suppressor gene, p53. The finding by Bochar et al. that BRCA1 is a crucial component of SWI/SNF, an 18-protein complex that remodels chromatin, now suggests how BRCA1 might regulate gene transcription.

Within the SWI/SNF complex, BRCA1 binds to a DNA-dependent ATPase called BRG1, the catalytic component that is essential for chromatin remodeling. If BRG1 is defective, BRCA1 is no longer able to switch on transcription of p53-responsive genes. Intriguingly, BRG1 binds to BRCA1 within the region encoded by exon 11, the section of the BRCA1 gene that harbors many of the predisposing cancer mutations identified so far. Now the search is on for mutations in BRG1 and other SWI/SNF proteins that also might predispose to cancer. — OMS

Cell 102, 257 (2000).

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