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RADX interacts with single-stranded DNA to promote replication fork stability.
Schubert, Lisa; Ho, Teresa; Hoffmann, Saskia; Haahr, Peter; Guérillon, Claire; Mailand, Niels.
Afiliación
  • Schubert L; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Ho T; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Hoffmann S; Center for Chromosome Stability, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Haahr P; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Guérillon C; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
  • Mailand N; Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
EMBO Rep ; 18(11): 1991-2003, 2017 11.
Article en En | MEDLINE | ID: mdl-29021206
Single-stranded DNA (ssDNA) regions form as an intermediate in many DNA-associated transactions. Multiple cellular proteins interact with ssDNA via the oligonucleotide/oligosaccharide-binding (OB) fold domain. The heterotrimeric, multi-OB fold domain-containing Replication Protein A (RPA) complex has an essential genome maintenance role, protecting ssDNA regions from nucleolytic degradation and providing a recruitment platform for proteins involved in responses to replication stress and DNA damage. Here, we identify the uncharacterized protein RADX (CXorf57) as an ssDNA-binding factor in human cells. RADX binds ssDNA via an N-terminal OB fold cluster, which mediates its recruitment to sites of replication stress. Deregulation of RADX expression and ssDNA binding leads to enhanced replication fork stalling and degradation, and we provide evidence that a balanced interplay between RADX and RPA ssDNA-binding activities is critical for avoiding these defects. Our findings establish RADX as an important component of cellular pathways that promote DNA replication integrity under basal and stressful conditions by means of multiple ssDNA-binding proteins.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN de Cadena Simple / Proteínas de Unión al ADN / Reparación del ADN / Replicación del ADN / Proteína de Replicación A Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN de Cadena Simple / Proteínas de Unión al ADN / Reparación del ADN / Replicación del ADN / Proteína de Replicación A Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido