ArticleMolecular cell2020
Cancer-Associated Gain-of-Function Mutations Activate a SWI/SNF-Family Regulatory Hub.
Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- The SMARCA4 subunit of the SWI/SNF complex prevents genome instability at G quadruplexes.Genome biology · 2026Article
- Tumor suppressor genes and KRAS G12C inhibitor resistance in non-small cell lung cancer.iScience · 2026Review
- New leap of BRD9 inhibitor: Imidazole substituents making BRD9 inhibitors excellent drug candidates for AML.Acta pharmaceutica Sinica. B · 2025Article
- Article
- A competitive regulatory mechanism of the Chd1 remodeler is integral to distorting nucleosomal DNA.Nature structural & molecular biology · 2025Article
- Article
- Phosphorylation regulates the chromatin remodeler SMARCAD1 in nucleosome binding, ATP hydrolysis, and histone exchange.The Journal of biological chemistry · 2024Article
- ISWI catalyzes nucleosome sliding in condensed nucleosome arrays.Nature structural & molecular biology · 2024Article
- Energy-driven genome regulation by ATP-dependent chromatin remodellers.Nature reviews. Molecular cell biology · 2024Review
- Targeting SWI/SNF Complexes in Cancer: Pharmacological Approaches and Implications.Epigenomes · 2024Review
- ISWI catalyzes nucleosome sliding in condensed nucleosome arrays.bioRxiv : the preprint server for biology · 2023Article
- Mechanism of action of the SWI/SNF family complexes.Nucleus (Austin, Tex.) · 2023Article
- A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodeler.Life science alliance · 2023Article
- (mis)-Targeting of SWI/SNF complex(es) in cancer.Cancer metastasis reviews · 2023Review
- Structural basis for TBP displacement from TATA box DNA by the Swi2/Snf2 ATPase Mot1.Nature structural & molecular biology · 2023Article
- Structure of nucleosome-bound human PBAF complex.Nature communications · 2022Article
- Structural mechanism of extranucleosomal DNA readout by the INO80 complex.Science advances · 2022Article
- BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma.Cancer discovery · 2022Article
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- Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
SWI/SNF-family remodelers (BAF/PBAF in mammals) are essential chromatin regulators, and mutations in human BAF/PBAF components are associated with ∼20% of cancers. Cancer-associated missense mutations in human BRG1 (encoding the catalytic ATPase) have been characterized previously as conferring loss-of-function. Here, we show that cancer-associated missense mutations in BRG1, when placed into the orthologous Sth1 ATPase of the yeast RSC remodeler, separate into two categories: loss-of-function enzymes, or instead, gain-of-function enzymes that greatly improve DNA translocation efficiency and nucleosome remodeling in vitro. Our work identifies a structural "hub," formed by the association of several Sth1 domains, that regulates ATPase activity and DNA translocation efficiency. Remarkably, all gain-of-function cancer-associated mutations and all loss-of-function mutations physically localize to distinct adjacent regions in the hub, which specifically regulate and implement DNA translocation, respectively. In vivo, only gain-of-function cancer-associated mutations conferred precocious chromatin accessibility. Taken together, we provide a structure-function mechanistic basis for cancer-associated hyperactivity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.