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Structure. 2015 Jul 7;23(7):1344-9. doi: 10.1016/j.str.2015.04.021. Epub 2015 Jun 11.

The SWI/SNF Subunit INI1 Contains an N-Terminal Winged Helix DNA Binding Domain that Is a Target for Mutations in Schwannomatosis.

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
2
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.
3
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. Electronic address: mxb@mrc-lmb.cam.ac.uk.

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.

PMID:
26073604
PMCID:
PMC4509781
DOI:
10.1016/j.str.2015.04.021
[Indexed for MEDLINE]
Free PMC Article

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