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 language | English |
|---|---|
| Pages (from-to) | 16783-16792 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 272 |
| Issue number | 27 |
| DOIs | |
| Publication status | Published - 1997 Jul 4 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Flexible DNA
T2 - Genetically unstable CTG·CAG and CGG·CCG from human hereditary neuromuscular disease genes
AU - Bacolla, Albino
AU - Gellibolian, Robert
AU - Shimizu, Miho
AU - Amirhaeri, Sorour
AU - Kang, Seong Man
AU - Ohshima, Keiichi
AU - Larson, Jacquelynn E.
AU - Harvey, Stephen C.
AU - Stollar, B. David
AU - Wells, Robert D.
PY - 1997/7/4
Y1 - 1997/7/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0030839912&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030839912&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.27.16783
DO - 10.1074/jbc.272.27.16783
M3 - Article
C2 - 9201983
AN - SCOPUS:0030839912
VL - 272
SP - 16783
EP - 16792
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 27
ER -