EXPANSION AND LENGTH-DEPENDENT FRAGILITY OF CTG REPEATS IN YEAST

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