Functional Restoration of BRCA1 Nonsense Mutations by Aminoglycoside-Induced Readthrough.

ABSTRACT: BRCA1 is a major tumor suppressor that functions in the accurate repair of DNA double-strand breaks via homologous recombination (HR). Nonsense mutations in BRCA1 lead to inactive truncated protein products and are associated with high risk of breast and ovarian cancer. These mutations generate premature termination codons (PTCs). Different studies have shown that aminoglycosides can induce PTC suppression by promoting stop codon readthrough and restoring full-length (FL) protein expression. The use of these compounds has been studied in clinical trials for genetic diseases such as cystic fibrosis and Duchenne muscular dystrophy, with encouraging results. Here we show proof-of-concept data demonstrating that the aminoglycoside G418 can induce BRCA1 PTC readthrough and restore

SUBMITTER: Abreu RBV 

PROVIDER: S-EPMC9273842 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature