Modulation of transcription reveals a new mechanism of triplet repeat instability in Escherichia coli

Many human hereditary disease genes are associated with the expansion of triplet repeat sequences. In Escherichia coli (CTG/CAG) triplet repeat sequences are unstable and we have developed a plasmid-based assay enabling us to observe and quantify both expansions and deletions. In this work, we have...

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Bibliographic Details
Published in:Journal of molecular biology 2001-03, Vol.307 (1), p.39-49
Main Authors: Schumacher, Sylvie, Pinet, Isabelle, Bichara, Marc
Format: Article
Language:English
Subjects:
Chemical Sciences
DNA, Bacterial - genetics
Escherichia coli
Escherichia coli - genetics
expansions
Gene Expression Regulation, Bacterial
Gene Silencing
instability
Life Sciences
Other
Plasmids - genetics
Repressor Proteins - biosynthesis
Repressor Proteins - physiology
Sequence Deletion
transcription
Transcription, Genetic
Trinucleotide Repeats - genetics
triplet repeats
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Summary:Many human hereditary disease genes are associated with the expansion of triplet repeat sequences. In Escherichia coli (CTG/CAG) triplet repeat sequences are unstable and we have developed a plasmid-based assay enabling us to observe and quantify both expansions and deletions. In this work, we have investigated the role of transcription on the instability of a (CTG/CAG) insert containing 64 repeats. Using this assay, we show that induction of transcription results in a significant increase in the frequency of long deletions and a reduction in the frequency of long expansions. On the other hand, overproduction of transcription repressor molecules leads to an increase in both expansions and deletions. In this latter case, we propose that the increased instability is due to the arrest of replication progression by the interaction of the repressor molecule with its cognate operator and subsequent generations of DNA strand breaks.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.2000.4489