title: Length and sequence heterozygosity differentially affect HRAS1 minisatellite stability during meiosis in yeast.
abstract: Minisatellites, one of the major classes of repetitive DNA sequences in eukaryotic genomes, are stable in somatic cells but destabilize during meiosis. We previously established a yeast model system by inserting the human Ha-ras/HRAS1 minisatellite into the HIS4 promoter and demonstrated that our system recapitulates all of the phenotypes associated with the human minisatellite. Here we demonstrate that meiotic minisatellite tract-length changes are half as frequent in diploid cells harboring heterozygous HRAS1 minisatellite tracts in which the two tracts differ by only two bases when compared to a strain with homozygous minisatellite tracts. Further, this decrease in alteration frequency is entirely dependent on DNA mismatch repair. In contrast, in a diploid strain containing heterozygous minisatellite tract alleles differing in length by three complete repeats, length alterations are observed at twice the frequency seen in a strain with homozygous tracts. Alterations consist of previously undetectable gene conversion events, plus nonparental length alteration events seen previously in strains with homozygous tracts. A strain containing tracts with both base and length heterozygosity exhibits the same level of alteration as a strain containing only length heterozygosity, indicating that base heterozygosity-dependent tract stabilization does not affect tract-length alterations occurring by gene conversion.
authors.affiliation: Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, 55455, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jauert
authors.forename: David T
authors.initials: DT
authors.lastname: Kirkpatrick
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D000619:Aminohydrolases / Q000235:genetics; D015825:Chromosomes, Fungal; D004271:DNA, Fungal; D017353:Gene Deletion; D011905:Genes, ras / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008540:Meiosis; D018598:Minisatellite Repeats / Q000235:genetics*; D008957:Models, Genetic; D009841:Oligonucleotides / Q000737:chemistry; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011755:Pyrophosphatases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D004271:DNA, Fungal; D009841:Oligonucleotides; D029701:Saccharomyces cerevisiae Proteins; D000429:Alcohol Oxidoreductases; C092116:HIS4 protein, S cerevisiae; D000619:Aminohydrolases; D011755:Pyrophosphatases