Document Detail

Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome.
MedLine Citation:
PMID:  9121457     Owner:  NLM     Status:  MEDLINE    
Trinucleotide repeat expansion is the causative mutation for a growing number of diseases including myotonic dystrophy, Huntington's disease, and fragile X syndrome. A (CTG/CAG)130 tract cloned from a myotonic dystrophy patient was inserted in both orientations into the genome of Saccharomyces cerevisiae. This insertion was made either very close to the 5' end or very close to the 3' end of a URA3 transcription unit. Regardless of its orientation, no evidence was found for triplet-mediated transcriptional repression of the nearby gene. However, the stability of the tract correlated with its orientation on the chromosome. In one orientation, the (CTG/CAG)130 tract was very unstable and prone to deletions. In the other orientation, the tract was stable, with fewer deletions and two possible cases of expansion detected. Analysis of the direction of replication through the region showed that in the unstable orientation the CTG tract was on the lagging-strand template and that in the stable orientation the CAG tract was on the lagging-strand template. The orientation dependence of CTG/CAG tract instability seen in this yeast system supports models involving hairpin-mediated polymerase slippage previously proposed for trinucleotide repeat expansion.
C H Freudenreich; J B Stavenhagen; V A Zakian
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular and cellular biology     Volume:  17     ISSN:  0270-7306     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-04-24     Completed Date:  1997-04-24     Revised Date:  2010-09-10    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2090-8     Citation Subset:  IM    
Department of Molecular Biology, Princeton University, New Jersey 08544, USA.
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MeSH Terms
Base Sequence
DNA Primers / genetics
DNA Replication / genetics
DNA, Recombinant / biosynthesis,  chemistry,  genetics
Gene Expression
Genome, Fungal*
Genome, Human
Minisatellite Repeats
Models, Genetic
Myotonic Dystrophy / enzymology,  genetics
Nucleic Acid Conformation
Plasmids / genetics
Polymerase Chain Reaction
Protein-Serine-Threonine Kinases / genetics
Saccharomyces cerevisiae / genetics*,  metabolism
Transcription, Genetic
Trinucleotide Repeats*
Grant Support
Reg. No./Substance:
0/DNA Primers; 0/DNA, Recombinant; EC 2.7.1.-/myotonic dystrophy protein kinase; EC Kinases

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