title: The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis.
abstract: SWI/SNF complexes use the energy of ATP hydrolysis to remodel chromatin. In mammals they play a central role in regulating gene expression during differentiation and proliferation. Mutations in SWI/SNF subunits are among the most frequent gene alterations in cancer. The INI1/hSNF5/SMARCB1 subunit is mutated in both malignant rhabdoid tumor, a highly aggressive childhood cancer, and schwannomatosis, a tumor-predisposing syndrome characterized by mostly benign tumors of the CNS. Here, we show that mutations in INI1 that cause schwannomatosis target a hitherto unidentified N-terminal winged helix DNA binding domain that is also present in the BAF45a/PHF10 subunit of the SWI/SNF complex. The domain is structurally related to the SKI/SNO/DAC domain, which is found in a number of metazoan chromatin-associated proteins.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Allen
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
authors.forename: Stefan M V
authors.initials: SM
authors.lastname: Freund
authors.affiliation: Centre for Advanced Cancer Therapies, Department of Microbiology, Cell and Tumour Biology and Science for Life Laboratory, Karolinska Institutet, Tomtebodavägen 23, Stockholm 171 65, Sweden.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zinzalla
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. Electronic address: mxb@mrc-lmb.cam.ac.uk.
authors.forename: Mark
authors.initials: M
authors.lastname: Bycroft
mesh_terms: D000595:Amino Acid Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009442:Neurilemmoma / Q000235:genetics*; D017253:Neurofibromatoses / Q000235:genetics*; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D000071796:SMARCB1 Protein; D012878:Skin Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors