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Meiotic instability of CAG repeat tracts occurs by double-strand break repair in yeast

By Craig Jankowski, Farooq Nasar and Dilip K. Nag

Abstract

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

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2000
OAI identifier: oai:pubmedcentral.nih.gov:15766
Provided by: PubMed Central
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