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      Expansion and length-dependent fragility of CTG repeats in yeast.

      Science (New York, N.Y.)
      Chromosome Breakage, Chromosome Fragility, Chromosomes, Fungal, metabolism, DNA Damage, DNA Repair, DNA Replication, DNA, Fungal, Electrophoresis, Gel, Pulsed-Field, Exodeoxyribonuclease V, Exodeoxyribonucleases, genetics, Gene Deletion, Genes, Fungal, Humans, Hydroxyurea, pharmacology, Recombination, Genetic, Saccharomyces cerevisiae, Transformation, Genetic, Trinucleotide Repeat Expansion, Trinucleotide Repeats

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          Abstract

          Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.

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