4 results on '"Laughton C"'
Search Results
2. Determination of DNA structural detail using radioprobing.
- Author
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Girard PM, Laughton C, and Nikjoo H
- Subjects
- DNA Damage, Electrons, G-Quadruplexes radiation effects, Models, Molecular, Monte Carlo Method, Software, DNA chemistry, Radiobiology methods
- Abstract
Purpose: To put radioprobing into context as a relatively new method of determining structural detail in deoxyribonucleic acid (DNA), and to review its use since first proposed in 1997. The key feature of the method is that, by experiment or simulation, a radionuclide such as iodine-125 ((125)I) is placed near the DNA at a known point relative to the DNA base sequence, and the number of resulting strand breaks in each nucleotide is determined. As the intensity of damage declines consistently with distance from the radionuclide, relative distances between the emitter and the nucleotides can be deduced, and hence potentially the topology or structural detail of the DNA. For simulation, appropriate software includes a Molecular Dynamics package, analysis and visualization tools, and a Monte Carlo track structure program., Conclusions: A review of published work and our own recent unpublished studies have shown that radioprobing is sufficiently sensitive and consistent to determine structural detail such as internal folding topology and flexing behavior, and can be applied to DNA or a DNA-protein complex in an approximation to its normal biological environment.
- Published
- 2012
- Full Text
- View/download PDF
3. Simulation of (125)I-based radioprobing experiments to study DNA quadruplex structure and topology.
- Author
-
Girard PM, Nikjoo H, and Laughton C
- Subjects
- DNA chemistry, DNA Cleavage radiation effects, Electrons, Guanine chemistry, Computer Simulation, DNA radiation effects, G-Quadruplexes radiation effects, Iodine Radioisotopes chemistry, Models, Molecular, Monte Carlo Method
- Abstract
Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a (125)I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004., Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted., Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted., Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.
- Published
- 2008
- Full Text
- View/download PDF
4. A method for radioprobing DNA structures using Auger electrons.
- Author
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Nikjoo H, Laughton CA, Terrissol M, Panyutin IG, and Goodhead DT
- Subjects
- Base Sequence, Computer Simulation, DNA Damage radiation effects, Electrophoresis, Genes, nef genetics, Iodine Radioisotopes, Models, Molecular, Molecular Sequence Data, Monte Carlo Method, Plasmids genetics, Biochemistry methods, Chemistry Techniques, Analytical methods, DNA chemistry, DNA ultrastructure, Electrons, Nucleic Acid Conformation
- Abstract
Purpose: To present a new method for radioprobing a DNA triple helix structure by Auger electrons emitted in the decay of 125I using theoretical/computational approaches., Materials and Methods: A Monte Carlo track structure method was used to simulate the damage to a triplex resulting from Auger electrons emitted in the decay of an incorporated 125I atom in plasmid DNA. Comparison of the theoretical frequency distributions of single-strand breaks induced on the Pu and Py strands with the experimental data and a knowledge of the distances from the strand breaks to the iodine provide information on the structures otherwise difficult to obtain with X-ray crystallography., Results: In comparing theoretical frequency distributions of single-strand breaks with the experimental data it is found that the results are very sensitive to the conformation of the triplex model used. It is found that the best fit to the experimental data results from using a hybrid triplex model, in which the base-step geometry is A-like, while the sugar puckers adopt the B-like C2'-endo conformation., Conclusions: The approach and technique presented here represent a valuable new addition to the methods available for DNA structure determination since they provide information on medium-range structure otherwize difficult to obtain in the absence of X-ray crystallography. It is concluded that currently accepted models for triplex structure are not optimal, and a modified structure is proposed that fits the radioprobing results better, while maintaining agreement with the fibre diffraction and NMR data. Although the method has proved to be very useful for scoring alternative trial solutions, further studies combining experimental data from multiple iodine positions with track structure modelling are required for directing structural optimization.
- Published
- 2000
- Full Text
- View/download PDF
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