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Reference: Mitson, M, Kelley, LA, Sternberg, MJ et al., (2011). Functional significance of mutations in the Snf2 domain of ATRX. Human molecular genetics, 20 (13), 2603-2610.Citable link to this page:


Functional significance of mutations in the Snf2 domain of ATRX.

Abstract: ATRX is a member of the Snf2 family of chromatin-remodelling proteins and is mutated in an X-linked mental retardation syndrome associated with alpha-thalassaemia (ATR-X syndrome). We have carried out an analysis of 21 disease-causing mutations within the Snf2 domain of ATRX by quantifying the expression of the ATRX protein and placing all missense mutations in their structural context by homology modelling. While demonstrating the importance of protein dosage to the development of ATR-X syndrome, we also identified three mutations which primarily affect function rather than protein structure. We show that all three of these mutant proteins are defective in translocating along DNA while one mutant, uniquely for a human disease-causing mutation, partially uncouples adenosine triphosphate (ATP) hydrolysis from DNA binding. Our results highlight important mechanistic aspects in the development of ATR-X syndrome and identify crucial functional residues within the Snf2 domain of ATRX. These findings are important for furthering our understanding of how ATP hydrolysis is harnessed as useful work in chromatin remodelling proteins and the wider family of nucleic acid translocating motors.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Accepted Manuscript Funder: Medical Research Council   Funder: National Institute for Health Research   Notes:This is the accepted manuscript version of the article. The final version is available online from Oxford University Press at:

Bibliographic Details

Publisher: Oxford University Press

Publisher Website:

Journal: Human molecular geneticssee more from them

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Issue Date: 2011


Urn: uuid:e920d7d4-7156-4996-9e2f-906cda39f47f

Source identifier: 134966

Eissn: 1460-2083


Issn: 0964-6906 Item Description

Type: Journal article;

Language: eng

Version: Accepted ManuscriptKeywords: Cell Line Animals Humans Insects Mental Retardation, X-Linked alpha-Thalassemia Translocation, Genetic DNA Helicases Ubiquitin-Protein Ligases Nuclear Proteins Sequence Alignment Enzyme Activation Amino Acid Sequence Protein Conformation Mutation Models, Molecular Molecular Sequence Data Protein Stability Tiny URL: pubs:134966


Autor: Mitson, M - - - Kelley, LA - - - Sternberg, MJ - - - Higgs, DR - institutionUniversity of Oxford Oxford, MSD, RDM, RDM Clinical L



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