Mutations occurring at the human minisatellite MS1 integrated in haploid yeast are similar to MS1 mutations in humans.
MS1 is one of the most variable minisatellites so far isolated from the human genome. We have previously reported an MS1 length-mutant frequency of 29.6% in overnight cultures of haploid yeast cells carrying a 1.35 kb MS1 allele. Here we present data on the instability of alleles with lengths ranging from 0.15 kb to 2.05 kb, which revealed a threshold of 0.75 kb, at and below which MS1 alleles were entirely stable. Larger alleles exhibited a length-related increase in mutation frequency. Chromosomal integration of various MS1 alleles, isolated from bacterial transformants, in haploid yeast cells also revealed a threshold for the onset of instability and a higher degree of mutability for longer alleles. DNA sequencing of alleles showed that the length changes were due to mutational events involving repeat units in the central region of MS1 which is composed of two variant repeat units only. The similarity between MS1 mutations in yeast and humans argues that yeast represents a suitable model organism for mechanistic studies on mutations occurring in human minisatellites.
Maleki
S
S
Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
Cederberg
H
H
Rannug
U
U
D000483:Alleles; D001483:Base Sequence; D004261:DNA Replication; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D018598:Minisatellite Repeats / Q000235:genetics*; D016296:Mutagenesis; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D013045:Species Specificity