Meiotic Instability of CAG Repeat Tracts Occurs by Double-Strand Break Repair in Yeast

Expansion of trinucleotide repeats is associated with a growing number of human diseases. The mechanism and timing of expansion of the repeat tract are poorly understood. In humans, trinucleotide repeats show extreme meiotic instability, and expansion of the repeat tract has been suggested to occur...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2000-02, Vol.97 (5), p.2134-2139
Main Authors: Jankowski, Craig, Nasar, Farooq, Nag, Dilip K.
Format: Article
Language:English
Subjects:
Alcohol Oxidoreductases
Alleles
Aminohydrolases
Biological Sciences
Chromosomes
Diploidy
DNA Damage
DNA probes
DNA Repair
DNA, Fungal
Fungal Proteins - genetics
Genetic mutation
Humans
Meiosis
Microsatellite repeats
Polymerase chain reaction
Pyrophosphatases
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae Proteins
Spores
Transcription Factors - genetics
Trinucleotide Repeats
Yeasts
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Summary:Expansion of trinucleotide repeats is associated with a growing number of human diseases. The mechanism and timing of expansion of the repeat tract are poorly understood. In humans, trinucleotide repeats show extreme meiotic instability, and expansion of the repeat tract has been suggested to occur in the germ-line mitotic divisions or postmeiotically during early divisions of the embryo. Studies in model organisms have indicated that polymerase slippage plays a major role in the repeat tract instability and meiotic instability is severalfold higher than the mitotic instability. We show here that meiotic instability of the CAG/CTG repeat tract in yeast is associated with double-strand break (DSB) formation within the repeated sequences, and that the DSB formation is dependent on the meiotic recombination machinery. The DSB repair results in both expansions and contractions of the CAG repeat tract.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.040460297