(CA/GT)(n) microsatellites affect homologous recombination during yeast meiosis

One of the most common microsatellites in eukaryotes consists of tandem arr ays of the dinucleotide GT. Although the study of the instability of such r epetitive DNA has been extremely fruitful over the last decade, no biologic al function has been demonstrated for these sequences. We investigated the genetic behavior of a region of the yeast Saccharomyces cerevisiae genome c ontaining a 39-CA/GT dinucleotide repeat sequence. When the microsatellite sequence was present at the ARG4 locus on homologous chromosomes, diploid c ells undergoing meiosis generated an excess of tetrads containing a convers ion of the region restricted to the region of the microsatellite close to t he recombination-initiation double-strand break. Moreover, whereas the repe titive sequence had no effect on the frequency of single crossover, its pre sence strongly stimulated the formation of multiple crossovers. The combine d data strongly suggest that numerous recombination events are restricted t o the initiation side of the microsatellite as though progression of the st rand exchange initiated at the ARG4 promoter locus was impaired by the repe titive sequence. This observation corroborates in vitro experiments that de monstrated that RecA-promoted strand exchange is inhibited by CA/GT dinucle otide tracts. Surprisingly, meiotic instability of the microsatellite was v ery high (>0.1 alterations per tetrad) in all the spores with parental and recombinant chromosomes.