Mutations at the human minisatellite MS32 integrated in yeast occur with high frequency in meiosis and involve complex recombination events |
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Authors: | H Appelgren H Cederberg and U Rannug |
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Institution: | (1) Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, S-10691 Stockholm, Sweden Fax: +46-8-6124004, SE |
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Abstract: | Minisatellites are composed of tandem repetitive DNA sequences and are present at many positions in the human genome. They
frequently mutate to new length alleles in the germline, by complex and incompletely understood recombination mechanisms which
may operate during meiosis. In several minisatellites the mutation events are restricted to one end of the repeat array, indicating
a possible association with elements that act in cis. Mutant alleles do not show exchange of flanking regions. To construct a model system suitable for further investigations
of the mutation process, we have integrated the human minisatellite MS32, flanked by synthetic markers, in the vicinity of
a meiotic recombination hot spot upstream of the LEU2 locus in the yeast Saccharomyces cerevisiae. Here we provide direct evidence for a meiotic origin of MS32 mutations. Mutation events were polarised towards both ends
of the minisatellite and varied from simple duplications and deletions to complex intra- and interallelic events. Interallelic
events were frequently accompanied by exchange of regions flanking the minisatellite. The results also support the notion
that cis-acting elements are involved in the mutational process. The fact that MS32 mutant structures are similar in yeast and human
shows that meiotic recombination plays a crucial role in both organisms and emphasises the usefulness of yeast strains harbouring
minisatellites as a model system for the study of minisatellite mutation.
Received: 1 March 1997 / Accepted: 16 May 1997 |
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Keywords: | Genomic instability Meiosis Minisatellite Recombination Yeast |
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