1 Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America, 2 School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States of America, 3 Department of Biology, Tufts University, Medford, Massachusetts, United States of America
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Although meiotic recombination has been much more studied than mitotic recombination, mitotic recombination is a universal property. Meiotic recombination rates are quite variable within the genome, with some chromosomal regions (hotspots) having much higher levels of exchange than other regions (coldspots). For mitotic recombination, although some types of DNA sequences are known to be associated with elevated recombination rates (highly-transcribed genes, inverted repeated sequences), relatively few hotspots have been described. In this report, we show that a 690 base pair region consisting of 230 copies of the (GAA)n•(TTC)n trinucleotide repeat stimulates mitotic crossovers in yeast 10,000-fold more strongly than an “average” yeast sequence. This sequence is a preferred site for chromosome breakage in stationary phase yeast cells. Our findings may be relevant to understanding the expansions of the (GAA)n•(TTC)n trinucleotide repeat tracts that are associated with the human disease Friedreich's ataxia.
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