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

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

Research output: Contribution to journalArticle

93 Citations (Scopus)

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
Externally publishedYes

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B-Form DNA
Neuromuscular Diseases
Inborn Genetic Diseases
Genes
DNA
Trinucleotide Repeats
Electrophoresis
Base Pairing
Nervous System Heredodegenerative Disorders
Neurodegenerative diseases
Agar Gel Electrophoresis
Cyclization
Electrophoresis, Gel, Two-Dimensional
Isomers
Sepharose
Polyacrylamide Gel Electrophoresis
Assays
Gels
Molecules
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Flexible DNA : Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes. / Bacolla, Albino; Gellibolian, Robert; Shimizu, Miho; Amirhaeri, Sorour; Kang, Seong Man; Ohshima, Keiichi; Larson, Jacquelynn E.; Harvey, Stephen C.; Stollar, B. David; Wells, Robert D.

In: Journal of Biological Chemistry, Vol. 272, No. 27, 04.07.1997, p. 16783-16792.

Research output: Contribution to journalArticle

Bacolla, A, Gellibolian, R, Shimizu, M, Amirhaeri, S, Kang, SM, Ohshima, K, Larson, JE, Harvey, SC, Stollar, BD & Wells, RD 1997, 'Flexible DNA: Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes', Journal of Biological Chemistry, vol. 272, no. 27, pp. 16783-16792. https://doi.org/10.1074/jbc.272.27.16783
Bacolla, Albino ; Gellibolian, Robert ; Shimizu, Miho ; Amirhaeri, Sorour ; Kang, Seong Man ; Ohshima, Keiichi ; Larson, Jacquelynn E. ; Harvey, Stephen C. ; Stollar, B. David ; Wells, Robert D. / Flexible DNA : Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 27. pp. 16783-16792.
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AU - Kang, Seong Man

AU - Ohshima, Keiichi

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