BRCA1 cancer gene plays pivotal role in DNA contr...( that only a tenth of human genes are a...)

"In essence, these complexes loosen or unwrap the DNA to allow different cellular processes access to the genes," Shiekhattar says. "What we found was that BRCA1 is associated with one of these complexes that unpackages DNA."

The protein in the SWI/SNF complex that BRCA1 directly interacts with is called BRG1. Of the 18 proteins that constitute SWI/SNF, BRG1 is thought to be the active center of the complex with the other proteins supporting its function in different ways.

"BRG1 itself is interesting to us, because mutations in BRG1, like mutations in BRCA1, may lead to cancer," Shiekhattar notes. "Mutations in BRCA1 and another gene, BRCA2, have been linked to a high percentage of familial breast and ovarian cancers, but these represent only a small percentage - perhaps 5 percent - of these cancers overall. It may be that mutations in SWI/SNF complex proteins - BRG1 in particular - account for the unexplained majority of these cancers."

Additionally, when Shiekhattar and his team looked to see what part of BRCA1 interacted with BRG1, they found the relevant region of the protein corresponded to a stretch of the BRCA1 gene called exon 11 - a portion of the gene in which a high number of cancer-linked mutations have been found. This observation tends to confirm the significance of the findings linking BRCA1 to BRG1 and the larger SWI/SNF complex. Also, most if not all of the BRCA1 found in cells occurs in the SWI/SNF complex, suggesting the primacy of this role for BRCA1.

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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-898-3716
The Wistar Institute
20-Jul-2000