Researchers Show How Mutations in DNA Packaging Machines (SWI/SNF Complexes) Can Cause Cancer

Like wrenches made of Legos, SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodeling complexes ( tighten or loosen DNA in our cells to control how genes are turned on and made into proteins. When assembled correctly, these complexes play a crucial role in the development of normal tissues, and when broken, they can lead to the development of cancer. These complexes are commonly disrupted by mutations in the genes that encode them--but how this leads to cancer is poorly understood. New research from the Children’s Medical Center Research Institute (CRI) at the University of Texas (UT) Southwestern ( has determined how mutations in two key SWI/SNF proteins, ARID1A and ARID1B, can drive cancer development by disrupting the assembly of SWI/SNF complexes. The study (, published online on September 7, 2020 in Nature Cancer, addresses fundamental questions about SWI/SNF biology, as well as therapeutic strategies designed to kill cancer cells by targeting this complex. The article is titled “Dual ARID1A/ARID1B Loss Leads to Rapid Carcinogenesis and Disruptive Redistribution of BAF complexes.” "While it is abundantly clear that SWI/SNF components are defective in almost all cancer types, it is still fuzzy how mutations in components lead to broken SWI/SNF complexes, and how broken complexes cause disease," says study leader Hao Zhu ( (photo), MD, an Associate Professor at CRI.
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