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Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA

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Abstract

Fourteen genetic neurodegenerative diseases and three fragile sites have been associated with the expansion of (CTG)n•(CAG)n, (CGG)n•(CCG)n, or (GAA)n•(TTC)n repeat tracts. Different models have been proposed for the expansion of triplet repeats, most of which presume the formation of alternative DNA structures in repeat tracts. One of the most likely structures, slipped strand DNA, may stably and reproducibly form within triplet repeat sequences. The propensity to form slipped strand DNA is proportional to the length and homogeneity of the repeat tract. The remarkable stability of slipped strand DNA may, in part, be due to loop-loop interactions facilitated by the sequence complementarity of the loops and the dynamic structure of three-way junctions formed at the loop-outs.

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Authors and Affiliations

  1. Laboratory of DNA Structure and Mutagenesis, Center for Genome Research, Institute of Biosciences and Technology, Texas A&M University System Health Sciences Center, 2121 West Holcombe Blvd., 77030-3303, Houston, TX, USA

    Richard R. Sinden, Vladimir N. Potaman, Elena A. Oussatcheva, Christopher E. Pearson, Yuri L. Lyubchenko & Luda S. Shlyakhtenko

  2. Department of Genetics, Hospital for Sick Children, 555 University Avenue, Elm Wing, Rm. 11-135, M5G 1X8, Toronto, Ontario, Canada

    Christopher E. Pearson

  3. Departments of Biology and Microbiology, Arizona State University, 85287-2701, Tempe, AZ, USA

    Yuri L. Lyubchenko & Luda S. Shlyakhtenko

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  1. Richard R. Sinden
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  2. Vladimir N. Potaman
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  3. Elena A. Oussatcheva
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  4. Christopher E. Pearson
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  5. Yuri L. Lyubchenko
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  6. Luda S. Shlyakhtenko
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Correspondence to Richard R. Sinden.

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Sinden, R.R., Potaman, V.N., Oussatcheva, E.A. et al. Triplet repeat DNA structures and human genetic disease: dynamic mutations from dynamic DNA. J Biosci 27, 53–65 (2002). https://doi.org/10.1007/BF02703683

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