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2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.
Trzaska, Carole; Amand, Séverine; Bailly, Christine; Leroy, Catherine; Marchand, Virginie; Duvernois-Berthet, Evelyne; Saliou, Jean-Michel; Benhabiles, Hana; Werkmeister, Elisabeth; Chassat, Thierry; Guilbert, Romain; Hannebique, David; Mouray, Anthony; Copin, Marie-Christine; Moreau, Pierre-Arthur; Adriaenssens, Eric; Kulozik, Andreas; Westhof, Eric; Tulasne, David; Motorin, Yuri; Rebuffat, Sylvie; Lejeune, Fabrice.
Afiliación
  • Trzaska C; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
  • Amand S; Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Laboratory Molecules of Communication and Adaptation of Microorganisms (MCAM), UMR 7245 CNRS-MNHN, 75005, Paris, France.
  • Bailly C; Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Laboratory Molecules of Communication and Adaptation of Microorganisms (MCAM), UMR 7245 CNRS-MNHN, 75005, Paris, France.
  • Leroy C; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
  • Marchand V; Next-Generation Sequencing Core Facility, UMS2008 IBSLor CNRS-Université de Lorraine-INSERM, BioPôle, 54505, Vandoeuvre-les-Nancy, France.
  • Duvernois-Berthet E; Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Laboratoire Physiologie Moléculaire et Adaptation (PhyMA), UMR7221 CNRS-MNHN, 75005, Paris, France.
  • Saliou JM; CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019, UMR 8204, CIIL­Centre d'Infection et d'Immunité de Lille, University of Lille, 59000, Lille, France.
  • Benhabiles H; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
  • Werkmeister E; Cellular Microbiology and Physics of Infection Group, Center for Infection and Immunity of Lille, CNRS UMR8204, INSERM U1019, Institut Pasteur de Lille, Lille Regional Univ. Hosp. Centr., Lille Univ., Lille, 59000, France.
  • Chassat T; Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.
  • Guilbert R; Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.
  • Hannebique D; Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.
  • Mouray A; Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.
  • Copin MC; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
  • Moreau PA; Univ. Lille, Fac. Pharmacie Lille, ULR 4515, LGCgE, Laboratoire de Génie Civil et géo-Environnement, 59000, Lille, France.
  • Adriaenssens E; Univ. Lille, CNRS, INSERM, CHU.Lille, Centre Oscar Lambert, UMR9020-UMR1277, CANTHER - Cancer Heterogeneity, Plasticity and Résistance to Therapies, 59000, Lille, France.
  • Kulozik A; Department of Pediatric Oncology, Hematology and Immunology, Children's Hospital and Hopp Children's Tumor Center Heidelberg, EMBL/Medical Faculty Molecular Medicine Partnership Unit, 69120, Heidelberg, Germany.
  • Westhof E; Architecture and Reactivity of RNA, Institute of Molecular and Cellular Biology of the CNRS UPR9002/University of Strasbourg, Strasbourg, 67084, France.
  • Tulasne D; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France.
  • Motorin Y; Ingénierie Moléculaire et Physiopathologie Articulaire, UMR7365, CNRS - Université de Lorraine, 54505, Vandoeuvre-les-Nancy, France.
  • Rebuffat S; Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique, Laboratory Molecules of Communication and Adaptation of Microorganisms (MCAM), UMR 7245 CNRS-MNHN, 75005, Paris, France.
  • Lejeune F; Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France. fabrice.lejeune@inserm.fr.
Nat Commun ; 11(1): 1509, 2020 03 20.
Article en En | MEDLINE | ID: mdl-32198346
Nonsense mutations cause about 10% of genetic disease cases, and no treatments are available. Nonsense mutations can be corrected by molecules with nonsense mutation readthrough activity. An extract of the mushroom Lepista inversa has recently shown high-efficiency correction of UGA and UAA nonsense mutations. One active constituent of this extract is 2,6-diaminopurine (DAP). In Calu-6 cancer cells, in which TP53 gene has a UGA nonsense mutation, DAP treatment increases p53 level. It also decreases the growth of tumors arising from Calu-6 cells injected into immunodeficient nude mice. DAP acts by interfering with the activity of a tRNA-specific 2'-O-methyltransferase (FTSJ1) responsible for cytosine 34 modification in tRNATrp. Low-toxicity and high-efficiency UGA nonsense mutation correction make DAP a good candidate for the development of treatments for genetic diseases caused by nonsense mutations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Codón sin Sentido / Descubrimiento de Drogas / 2-Aminopurina / Mutación Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos de Selección de Medicamentos Antitumorales / Codón sin Sentido / Descubrimiento de Drogas / 2-Aminopurina / Mutación Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido