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CTG Triplet Repeats from the Myotonic Dystrophy Gene are Expanded inEscherichia coliDistal to the Replication Origin as a Single Large Event

1996; Elsevier BV; Volume: 258; Issue: 4 Linguagem: Inglês

10.1006/jmbi.1996.0266

1089-8638

Seongman Kang, Keiichi Ohshima, Adam Jaworski, Robert D. Wells,

Microtubule and mitosis dynamics

The expansion and contraction of CTG and CGG trinucleotide repeat sequences have been associated with several heritable genetic diseases. We developed a system for investigating the expansion of triplet repeat sequences inEscherichia coliin order to elucidate molecular mechanisms. Analysis of expanded regions using the interrupting CTA triplet sequence as a location marker within the CTG tract revealed that the expansion of large CTG repeats is one event rather than an accumulation of multiple small expansions and that the expansions occur more frequently in the region distal from the replication origin. Also, we showed that a loss of interruptions increases the expansion frequency. Thus, the instability of large triplet repeats in hereditary diseases occurs by a mechanism different from the instability in microsatellite sequences caused by defects in mismatch repair systems for certain sporadic cancers and hereditary non-polyposis colorectal cancers.