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.