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Vol. 14, No. 10, pp. 1261-1268, May 15, 2000
1 UMR-CNRS 2027, Institut Curie-Section de Recherche,
Université Paris-Sud, F-91405 Orsay, France; 2 UMR-CNRS
144, Institut Curie-Section de Recherche, F-75248 Paris Cedex 05, France
One of the most common microsatellites in eukaryotes consists of
tandem arrays of the dinucleotide GT. Although the study of the
instability of such repetitive DNA has been extremely fruitful over the
last decade, no biological function has been demonstrated for these
sequences. We investigated the genetic behavior of a region of the
yeast Saccharomyces cerevisiae genome containing a
39-CA/GT dinucleotide repeat sequence. When the
microsatellite sequence was present at the ARG4 locus on
homologous chromosomes, diploid cells undergoing meiosis generated an
excess of tetrads containing a conversion of the region restricted to
the region of the microsatellite close to the recombination-initiation
double-strand break. Moreover, whereas the repetitive sequence had no
effect on the frequency of single crossover, its presence strongly
stimulated the formation of multiple crossovers. The combined data
strongly suggest that numerous recombination events are restricted to
the initiation side of the microsatellite as though progression of the
strand exchange initiated at the ARG4 promoter locus was
impaired by the repetitive sequence. This observation corroborates in
vitro experiments that demonstrated that RecA-promoted strand exchange is inhibited by CA/GT dinucleotide tracts. Surprisingly,
meiotic instability of the microsatellite was very high (>0.1
alterations per tetrad) in all the spores with parental and recombinant chromosomes.
[Key Words: Microsatellite; homologous recombination; double-strand break repair; genome instability; meiosis; Saccharomyces cerevisiae]
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