CTG TRIPLET REPEATS FROM THE MYOTONIC-DYSTROPHY GENE ARE EXPANDED IN ESCHERICHIA-COLI DISTAL TO THE REPLICATION ORIGIN AS A SINGLE LARGE EVENT

The expansion and contraction of CTG and CGG trinucleotide repeat sequ ences have been associated with several heritable genetic diseases. We developed a system for investigating the expansion of triplet repeat sequences in Escherichia coli in order to elucidate molecular mechanis ms. Analysis of expanded regions using the interrupting CTA triplet se quence as a location marker within the CTG tract revealed that the exp ansion of large CTG repeats is one event rather than an accumulation o f multiple small expansions and that the expansions occur more frequen tly in the region distal from the replication origin. Also, we showed that a loss of interruptions increases the expansion frequency Thus, t he instability of large triplet repeats in hereditary diseases occurs by a mechanism different from the instability in microsatellite sequen ces caused by defects in mismatch repair systems for certain sporadic cancers and hereditary non-polyposis colorectal cancers. (C) 1996 Acad emic Press Limited