Article

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

Laboratoire de Génétique Moléculaire, Signalisation et Cancer Unité Mixte de Recherche 5201 Centre National de la Recherche Scientifique, Université Claude Bernard Lyon I, Lyon, France.
Human Mutation (impact factor: 5.69). 11/2006; 27(10):1024-9. DOI:10.1002/humu.20384 pp.1024-9
Source: PubMed

ABSTRACT 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.

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Keywords

185delAG mutation
 
BRCA1 gene
 
BRCA1 minigenes
 
coding sequence [Perrin-Vidoz
 
founder Jewish Ashkenazi mutation
 
HeLa cells
 
introduce premature termination codons
 
mutation
 
nonsense-mediated mRNA decay
 
ovarian cancer patients
 
protein expression
 
PTC
 
PTCs
 
thousands
 
transcripts bearing
 
translation reinitiation
 
truncating mutations
 
two mutations