2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.

2-Aminopurine / analogs & derivatives Animals Codon, Nonsense / drug effects Disease Models, Animal Drug Discovery Drug Screening Assays, Antitumor Gene Expression Regulation, Neoplastic / drug effects Genes, p53 / genetics HEK293 Cells HeLa Cells Humans Lepisma / chemistry Mice Mice, Nude Mutation / drug effects RNA, Transfer / genetics tRNA Methyltransferases / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 03 2020
Historique:
received: 24 01 2019
accepted: 21 02 2020
entrez: 22 3 2020
pubmed: 22 3 2020
medline: 18 7 2020
Statut: epublish

Résumé

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 tRNA

Identifiants

DOI: 10.1038/s41467-020-15140-z PMID: 32198346 PMC: PMC7083880
pubmed: 32198346
doi: 10.1038/s41467-020-15140-z
pii: 10.1038/s41467-020-15140-z
pmc: PMC7083880
doi:

Substances chimiques

Codon, Nonsense 0
2-Aminopurine 452-06-2
2,6-diaminopurine 49P95BAU4Z
RNA, Transfer 9014-25-9
tRNA Methyltransferases EC 2.1.1.-
Ftsj1 protein, mouse EC 2.1.1.205

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1509

Références

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Auteurs

Carole 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.

Séverine 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.

Christine 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.

Catherine 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.

Virginie Marchand (V)

Next-Generation Sequencing Core Facility, UMS2008 IBSLor CNRS-Université de Lorraine-INSERM, BioPôle, 54505, Vandoeuvre-les-Nancy, France.
ORCID: 0000-0002-8537-1139

Evelyne 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.
ORCID: 0000-0003-1442-6603

Jean-Michel Saliou (JM)

CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019, UMR 8204, CIIL‑Centre d'Infection et d'Immunité de Lille, University of Lille, 59000, Lille, France.
ORCID: 0000-0003-0105-5196

Hana 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.

Elisabeth 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.

Thierry Chassat (T)

Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.

Romain Guilbert (R)

Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.

David Hannebique (D)

Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.

Anthony Mouray (A)

Institut Pasteur de Lille - PLEHTA (Plateforme d'expérimentation et de Haute Technologie Animale), 59019, Lille, France.

Marie-Christine 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.

Pierre-Arthur Moreau (PA)

Univ. Lille, Fac. Pharmacie Lille, ULR 4515, LGCgE, Laboratoire de Génie Civil et géo-Environnement, 59000, Lille, France.
ORCID: 0000-0003-4783-3643

Eric Adriaenssens (E)

Univ. Lille, CNRS, INSERM, CHU.Lille, Centre Oscar Lambert, UMR9020-UMR1277, CANTHER - Cancer Heterogeneity, Plasticity and Résistance to Therapies, 59000, Lille, France.

Andreas 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.
ORCID: 0000-0003-1953-0848

Eric Westhof (E)

Architecture and Reactivity of RNA, Institute of Molecular and Cellular Biology of the CNRS UPR9002/University of Strasbourg, Strasbourg, 67084, France.

David 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.

Yuri Motorin (Y)

Ingénierie Moléculaire et Physiopathologie Articulaire, UMR7365, CNRS - Université de Lorraine, 54505, Vandoeuvre-les-Nancy, France.
ORCID: 0000-0002-8018-334X

Sylvie 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.

Fabrice 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.
ORCID: 0000-0002-5132-3585

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Classifications MeSH

questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Purines › Adénine › Amino-2 purine › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Eucaryotes › Animaux › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Codon non-sens › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Tests de criblage d'agents antitumoraux › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Gènes suppresseurs de tumeur › Gènes p53 › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HeLa › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Eucaryotes › Animaux › Invertébrés › Arthropodes › Insectes › Lepisma › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris nude › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN de transfert › 2,6-Diaminopurine as a highly potent corrector...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › T-RNA methyltransferases › 2,6-Diaminopurine as a highly potent corrector...