Meiotic interallelic conversion at the human minisatellite MS32 in yeast triggers recombination in several chromatids

Tandem repetitive DNA sequences such as minisatellites include the most polymorphic loci yet identified in the human genome. The high mutation rates at many of these loci are driven by incompletely understood recombination-based mechanisms that operate in the germline. To analyse aspects of minisatellite mutation processes and general eukaryotic recombination in meiosis that cannot be studied in humans or other mammals, including crosstalk and interplay between all four chromatids, we have previously constructed a eukaryotic model system, enabling the analysis of all four products of meiosis. In this system we have integrated alleles of the human minisatellite MS32, flanked by synthetic markers, in the vicinity of a meiotic recombination hot spot in chromosome III of Saccharomyces cerevisiae. In the present study, tetrad analysis showed that gene conversion is the predominant and possibly the universal pathway leading to interallelic transfer of repeats, with or without exchange of flanking regions. The data also suggest a hyper-recombinogenic state, triggered by interallelic mutation processes which generate a cascade of mutant alleles in the same meiosis. A number of tetrads contained identical mutant alleles of meiotic origin. Several tetrads could not be explained by the current models for minisatellite mutation. Accordingly, we here present a modified model based on the successive repair of multiple double-strand breaks.