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Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae.

ABSTRACT: Expansions of trinucleotide GAA•TTC tracts are associated with the human disease Friedreich's ataxia, and long GAA•TTC tracts elevate genome instability in yeast. We show that tracts of (GAA)(230)•(TTC)(230) stimulate mitotic crossovers in yeast about 10,000-fold relative to a "normal" DNA sequence; (GAA)(n)•(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)(n)•(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)(n)•(TTC)(n) tracts can be a potent source of loss of heterozygosity in yeast.

SUBMITTER: Tang W

PROVIDER: S-EPMC3020933 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae.

Tang Wei W Dominska Margaret M Greenwell Patricia W PW Harvanek Zachary Z Lobachev Kirill S KS Kim Hyun-Min HM Narayanan Vidhya V Mirkin Sergei M SM Petes Thomas D TD

PLoS genetics 20110113 1

Expansions of trinucleotide GAA•TTC tracts are associated with the human disease Friedreich's ataxia, and long GAA•TTC tracts elevate genome instability in yeast. We show that tracts of (GAA)(230)•(TTC)(230) stimulate mitotic crossovers in yeast about 10,000-fold relative to a "normal" DNA sequence; (GAA)(n)•(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 conv ...[more]

PMID: 21249181

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