Expansion and Length-Dependent Fragility of CTG Repeats in Yeast

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Science  06 Feb 1998:
Vol. 279, Issue 5352, pp. 853-856
DOI: 10.1126/science.279.5352.853

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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 inSaccharomyces 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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