2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32198346.
- Also identified by DOI 10.1038/s41467-020-15140-z and PMC identifier 7083880.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 tRNA<sup>Trp</sup>. 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.
Medical subject headings
- 2-Aminopurine
- Codon, Nonsense
- Drug Discovery
- Drug Screening Assays, Antitumor
- Mutation