2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.
Nat Commun
; 11(1): 1509, 2020 03 20.
Article
em En
| MEDLINE
| ID: mdl-32198346
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ensaios de Seleção de Medicamentos Antitumorais
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Códon sem Sentido
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Descoberta de Drogas
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2-Aminopurina
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Mutação
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2020
Tipo de documento:
Article