The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon

Hum Mutat. 2006 Oct;27(10):1024-9. doi: 10.1002/humu.20384.


The 185delAG mutation (c.68_69delAG; ter39) in the BRCA1 gene is a founder Jewish Ashkenazi mutation that is carried by 1% of this population and has been identified in thousands of breast or ovarian cancer patients. We have previously described that transcripts bearing this mutation, as well as transcripts bearing the 188del11 mutation (c.71_81del; ter36), are not degraded by nonsense-mediated mRNA decay (NMD), contrary to our observations of other truncating mutations that introduce premature termination codons (PTCs) farther downstream in the coding sequence [Perrin-Vidoz et al., 2002]. To test the hypothesis that these two mutations fail to trigger NMD because of translation reinitiation, we have constructed BRCA1 minigenes and studied their protein expression after transient expression in HeLa cells. We show here that in the presence of a (PTC) at position 36 or 39, translation reinitiation occurs in the BRCA1 minigenes at position 128.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • Base Sequence
  • Blotting, Northern / methods
  • Blotting, Western / methods
  • Codon, Initiator / genetics*
  • Codon, Nonsense / genetics
  • HeLa Cells
  • Humans
  • Models, Genetic
  • Mutation / genetics*
  • Plasmids / genetics
  • Protein Biosynthesis / genetics*
  • Sequence Deletion
  • Transfection / methods


  • BRCA1 Protein
  • Codon, Initiator
  • Codon, Nonsense