A method for radioprobing DNA structures using Auger electrons

Citation
H. Nikjoo et al., A method for radioprobing DNA structures using Auger electrons, INT J RAD B, 76(12), 2000, pp. 1607-1615
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Experimental Biology
Journal title
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
ISSN journal
0955-3002 → ACNP
Volume
76
Issue
12
Year of publication
2000
Pages
1607 - 1615
Database
ISI
SICI code
0955-3002(200012)76:12<1607:AMFRDS>2.0.ZU;2-A
Abstract
Purpose: To present a new method for radioprobing a DNA triple helix struct ure by Auger electrons emitted in the decay of I-125 using theoretical/comp utational approaches. Materials and methods: A Monte Carlo track structure method was used to sim ulate the damage to a tripler resulting from Auger electrons emitted in the decay of an incorporated I-125 atom in plasmid DNA. Comparison of the theo retical frequency distributions of single-strand breaks induced on the Pu a nd Py strands with the experimental data and a knowledge of the distances f rom the strand breaks to the iodine provide information on the structures o therwise 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 sen sitive to the conformation of the tripler model used. It is found that the best fit to the experimental data results from using a hybrid tripler 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 sinc e they provide information on medium-range structure otherwise difficult to obtain in the absence of X-ray crystallography. It is concluded that curre ntly accepted models for tripler structure are not optimal, and a modified structure is proposed that fits the radioprobing results better, while main taining agreement with the fibre diffraction and NMR data. Although the met hod has proved to be very useful for scoring alternative trial solutions, f urther studies combining experimental data from multiple iodine positions w ith track structure modelling are required for directing structural optimiz ation.