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dc.contributor.author
Tuengler, Victoria
dc.contributor.author
Wolfgang, Staroske
dc.contributor.author
Kind, Barbara
dc.contributor.author
Dobrick, Manuela
dc.contributor.author
Kretschmer, Stefanie
dc.contributor.author
Schmidt, Franziska
dc.contributor.author
Krug, Claudia
dc.contributor.author
Lorenz, Mike
dc.contributor.author
Chara, Osvaldo
dc.contributor.author
Schwille, Petra
dc.contributor.author
Lee-Kirsch, Min Ae
dc.date.available
2017-09-13T15:05:42Z
dc.date.issued
2013-06
dc.identifier.citation
Tuengler, Victoria; Wolfgang, Staroske; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; et al.; Single-stranded nucleic acids promote SAMHD1 complex formation; Springer; Journal of Molecular Medicine (Berlin, Germany); 91; 6; 6-2013; 759-770
dc.identifier.issn
0946-2716
dc.identifier.uri
http://hdl.handle.net/11336/24122
dc.description.abstract
SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi–Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Samhd1
dc.subject
Aicardi–Goutières Syndrome
dc.subject
Fluorescence Cross-Correlation Spectroscopy
dc.subject
Nucleic Acids
dc.subject.classification
Bioquímica y Biología Molecular
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Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Single-stranded nucleic acids promote SAMHD1 complex formation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-09-01T17:44:58Z
dc.journal.volume
91
dc.journal.number
6
dc.journal.pagination
759-770
dc.journal.pais
Alemania
dc.journal.ciudad
Berlin
dc.description.fil
Fil: Tuengler, Victoria. Technische Universität Dresden; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Wolfgang, Staroske. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Kind, Barbara. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Dobrick, Manuela. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Kretschmer, Stefanie. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Schmidt, Franziska. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Krug, Claudia. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Lorenz, Mike. Max Planck Institute of Molecular Cell Biology and Genetics; Alemania
dc.description.fil
Fil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Technische Universität Dresden; Alemania
dc.description.fil
Fil: Schwille, Petra. Max Planck Institute Of Biochemistry; Alemania
dc.description.fil
Fil: Lee-Kirsch, Min Ae. Technische Universität Dresden; Alemania
dc.journal.title
Journal of Molecular Medicine (Berlin, Germany)
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00109-013-0995-3
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00109-013-0995-3
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