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

被引：36

作者：

Allen, Mark D. ^{[1
]}

Freund, Stefan M. V. ^{[1
]}

Zinzalla, Giovanna ^{[2
,3
]}

Bycroft, Mark ^{[1
]}

机构：

[1] MRC Lab Mol Biol, Cambridge CB2 0QH, England

[2] Karolinska Inst, Ctr Adv Canc Therapies, Dept Microbiol Cell & Tumour Biol, S-17165 Stockholm, Sweden

[3] Karolinska Inst, Sci Life Lab, S-17165 Stockholm, Sweden

来源：

STRUCTURE | 2015年 / 23卷 / 07期

基金：

英国医学研究理事会;

关键词：

FAMILIAL SCHWANNOMATOSIS; CRYSTAL-STRUCTURE; SPORADIC SCHWANNOMATOSIS; MULTIPLE MENINGIOMAS; SMARCB1; MUTATION; STRUCTURAL BASIS; COMPLEX; REVEALS; TRANSCRIPTION; RECOGNITION;

D O I：

10.1016/j.str.2015.04.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1344 / 1349

页数：6

共 32 条

[1] Gapped BLAST and PSI-BLAST: a new generation of protein database search programs [J].