Friedreich's ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae.
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.
Department of Molecular Genetics and Microbiology, Duke University, Durham, North Carolina, United States of America.
Wei
W
Tang
Margaret
M
Dominska
Patricia W
PW
Greenwell
Zachary
Z
Harvanek
Kirill S
KS
Lobachev
Hyun-Min
HM
Kim
Vidhya
V
Narayanan
Sergei M
SM
Mirkin
Thomas D
TD
Petes
D015825:Chromosomes, Fungal; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D005785:Gene Conversion; D008938:Mitosis; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D018911:Trinucleotide Repeats
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