2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.
Fiche publication
Date publication
mars 2020
Journal
Nature communications
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MOTORINE Iouri, Dr MARCHAND Virginie
Tous les auteurs :
Trzaska C, Amand S, Bailly C, Leroy C, Marchand V, Duvernois-Berthet E, Saliou JM, Benhabiles H, Werkmeister E, Chassat T, Guilbert R, Hannebique D, Mouray A, Copin MC, Moreau PA, Adriaenssens E, Kulozik A, Westhof E, Tulasne D, Motorin Y, Rebuffat S, Lejeune F
Lien Pubmed
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. 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.
Référence
Nat Commun. 2020 Mar 20;11(1):1509