Scientists have created an unprecedented 3-dimensional structural model of a key molecular “machine” known as the BAF complex (mammalian SWI/SNF complex) (https://en.wikipedia.org/wiki/SWI/SNF), which modifies DNA architecture and is frequently mutated in cancer and some other diseases. The researchers, led by Cigall Kadoch (photo), PhD, (http://www.kadochlab.org/ of Dana-Farber Cancer Institute, have reported the first 3-D structural “picture” of BAF complexes purified directly from human cells in their native states--rather than artificially synthesized in the laboratory--providing an opportunity to spatially map thousands of cancer-associated mutations to specific locations within the complex. “A 3-D structural model, or ‘picture,’ of how this complex actually looks inside the nucleus of our cells has remained elusive--until now,” says Dr. Kadoch. The newly obtained model represents “the most complete picture of the human BAF complex achieved to date,” said the investigators, reporting in the journal Cell. The article is titled “A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms.” Dr. Kadoch is Associate Professor of Pediatric Oncology, Dana-Farber Cancer Institute; Affiliated Faculty, Biological Chemistry and Molecular Pharmacology, Harvard Medical School; and Institute Member and Epigenomics Program Co-Director, Broad Institute of MIT and Harvard. The new findings “provide a critical foundation for understanding human disease-associated mutations in components of the BAF complex, which are present in over 20% of human cancers and in several intellectual disability and neurodevelopomental disorders,” the authors said.
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