Restoring BRCA1 Function With Antibiotics
Abstract
BRCA2 mutations leading to premature termination of the protein confer high cancer risk. Currently very few clinical options are possible for women carrying predisposing mutations. So far, the only one to provide a significant reduction in risk is prophylactic mastectomy and oopherectomy. Restoring BRCAl function in these patients might result in a significant decrease in cancer risk. We proposed to restore BRCAl function using antibiotics. In eukaryotic cells, aminoglycosides interact with ribosomal RNA and relaxes codon recognition allowing normal tRNAs to insert an amino acid at a codon specifying a stop. As a result, the ribosome will read through the mutation and produce a full-length protein that can potentially restore the protein's original function. We focused on the following aims: Screen aminoglycosides in yeast to determine if they could suppress a nonsense mutation in BRCAl; Determine the ability of selected antibiotics in human cells to suppress different types of mutations and on the wild type BRCAl. We show that gentamicin suppresses BRCAl nonsense mutations is able to restore some of the wildtype protein levels and may provide a preventive strategy for individuals carrying these mutations. Given the dearth of alternatives for these individuals and the results obtained in our studies the use of antibiotics merits further investigation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2003
- Accession Number
- ADA420394
Entities
People
- Alvaro N. Monteiro