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 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.
Jankowski
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Molecular Genetics Program, Wadsworth Center, 120 New Scotland Avenue, Albany, NY 12201-2002, USA.
Nasar
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Nag
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D000429:Alcohol Oxidoreductases; D000619:Aminohydrolases; D004249:DNA Damage; D004260:DNA Repair; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D008540:Meiosis; D011755:Pyrophosphatases; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics; D018911:Trinucleotide Repeats
D004271:DNA, Fungal; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000429:Alcohol Oxidoreductases; C092116:HIS4 protein, S cerevisiae; D000619:Aminohydrolases; D011755:Pyrophosphatases