friedreichs ataxia (gaa)n？(ttc)n repeats strongly stimulate mitotic crossovers in saccharomyces cerevisae弗里德希氏共济失调(棉酚)n (ttc)n重复强烈刺激有丝分裂在酿酒cerevisae跨界车.pdfVIP

Friedreich’s Ataxia (GAA) N(TTC) Repeats Strongly n n Stimulate Mitotic Crossovers in Saccharomyces cerevisae 1 1 1 1 2 Wei Tang , Margaret Dominska , Patricia W. Greenwell , Zachary Harvanek , Kirill S. Lobachev , 2¤ 2 3 1 Hyun-Min Kim , Vidhya Narayanan , Sergei M. Mirkin , Thomas D. Petes * 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 Abstract Expansions of trinucleotide GAANTTC tracts are associated with the human disease Friedreich’s ataxia, and long GAANTTC tracts elevate genome instability in yeast. We show that tracts of (GAA)230N(TTC)230 stimulate mitotic crossovers in yeast about 10,000-fold relative to a ‘‘normal’’ DNA sequence; (GAA)nN(TTC)n tracts, however, do not significantly elevate meiotic recombination. Most of the mitotic crossovers are associated with a region of non-reciprocal transfer of information (gene conversion). The major class of recombination events stimulated by (GAA)nN(TTC)n tracts is a tract-associated double-strand break (DSB) that occurs in unreplicated chromosomes, likely in G1 of the cell cycle. These findings indicate that (GAA)nN(TTC)n tracts can be