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In 2013, Broad Institute member Cigall Kadoch, then a postdoctoral researcher at Stanford University, discovered that approximately 20 percent of all human cancers involve mutations in a group of proteins called BAF, a complex that is also linked to intellectual disability and autism spectrum disorders. However, little has been known about the structure of these complexes, and how they contribute to disease.
Now, a team of researchers led by Kadoch, provides a detailed blueprint of how the individual parts of this key protein complex fit together, an insight that could lead to new advances in drug discovery.
Work - Barrier - Understanding - Disease - Mutations
"This work overcomes a major barrier in the mechanistic understanding of disease mutations as well as drug discovery efforts," said senior author Kadoch, who co-directs the Broad Epigenomics Program and is an assistant professor of pediatric oncology at the Dana-Farber Cancer Institute and Harvard Medical School.
Reporting in Cell, the authors shed new light on how these BAF complexes are structured and organized. And knowing a protein's structure is key to understanding its function.
BAF - Complexes - Architecture - Chromatin - Packaging
BAF complexes control the architecture of chromatin, the packaging entity made up of DNA and proteins inside each cell's nucleus, and regulate gene activity. BAF was first discovered in yeast, subsequently...
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