Flexible DNA: Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes

Albino Bacolla, Robert Gellibolian, Miho Shimizu, Sorour Amirhaeri, Seongman Kang, Keiichi Ohshima, Jacquelynn E. Larson, Stephen C. Harvey, B. David Stollar, Robert D. Wells

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Abstract

The properties of duplex CTG·CAG and CGG·CCG, which are involved in the etiology of several hereditary neurodegenerative diseases, were investigated by a variety of methods, including circularization kinetics, apparent helical repeat determination, and polyacrylamide gel electrophoresis. The bending moduli were 1.13 x 10-19 erg · cm for CTG and 1.27 x 10-19 erg · cm for CGG, 40% less than for random B-DNA. Also, the persistence lengths of the triplet repeat sequences were ~60% the value for random B-DNA. However, the torsional moduli and the helical repeats were 2.3 x 10-19 erg · cm and 10.4 base pairs (bp)/turn for CTG and 2.4 x 10- 19 erg · cm and 10.3 hp/turn for CGG, respectively, all within the range for random B-DNA. Determination of the apparent helical repeat by the band shift assay indicated that the writhe of the repeats was different from that of random B-DNA. In addition, molecules of 224-245 bp in length (64-71 triplet repeats) were able to form topological isomers upon cyclization. The low bending moduli are consistent with predictions from crystallographic variations in slide, roll, and tilt. No unpaired bases or non-B-DNA structures could be detected by chemical and enzymatic probe analyses, two- dimensional agarose gel electrophoresis, and immunological studies. Hence, CTG and CGG are more flexible and highly writhed than random B-DNA and thus would be expected to act as sinks for the accumulation of superhelical density.

Original languageEnglish
Pages (from-to)16783-16792
Number of pages10
JournalJournal of Biological Chemistry
Volume272
Issue number27
DOIs
Publication statusPublished - 1997 Jul 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Bacolla, A., Gellibolian, R., Shimizu, M., Amirhaeri, S., Kang, S., Ohshima, K., Larson, J. E., Harvey, S. C., Stollar, B. D., & Wells, R. D. (1997). Flexible DNA: Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes. Journal of Biological Chemistry, 272(27), 16783-16792. https://doi.org/10.1074/jbc.272.27.16783