Monte Carlo Approach in Assessing Damage in Higher Order Structures of DNA
We have developed a computer model of nuclear DNA in the form of chromatin fiber. The fibers are modeled as an ideal solenoid consisting of twenty helical turns with six nucleosomes per turn. The chromatin model, in combination with our Monte Carlo theory of radiation damage induced by charged particles, based on general features of track structure and stopping power theory, has been used to evaluate the influence of DNA structure on initial damage. An interesting feature has emerged from our calculations. Our calculated results predict the existence of strong spatial correlations in damage sites associated with the symmetries in the solenoidal model. We have calculated spectra of short fragments of double stranded DNA produced by multiple double strand breaks induced by both high and low LET radiation. The spectra exhibit peaks at multiples of ~85 base pairs (the nucleosome periodicity), and ~ 1000 base pairs (solenoid periodicity). Preliminary experiments to investigate the fragment distributions from irradiated DNA, made by B. Rydberg at Lawrence Berkeley Laboratory, confirm the existence of short DNA fragments and are in substantial agreement with the predictions of our theory.
KeywordsStrand Break Double Strand Break Short Fragment Chromatin Fiber Track Structure
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- 2.A. Chatterjee and W. R. Holley, A general theory of DNA strand break production by direct and indirect effects, Radiation Protection Dosimetry, 31, 241–247 (1990).Google Scholar
- 3.A. Chatterjee and W.R. Holley, Biochemical Mechanisms and Clusters of Damage for High-LET Radiation,Adv. Space. Res. 16, (2) 33-(2) 33-(2)43 (1992).Google Scholar
- 4.J. B. Schmidt, Heavy Ion Induced Lesions in DNA: A Theoretical Model for the Initial Induction of DNA Strand Breaks and Chromatin Breaks, Ph. D. Thesis, University of California, Berkeley (1993).Google Scholar
- 5.A. Chatterjee and W. R. Holley, Early chemical events and initial DNA damage, in Physical and Chemical Mechanisms in Molecular Radiation Biology, eds. W. A. Glass and M. N. Varma, Plenum Press, New York, 1991.Google Scholar
- 8.A. Mozumder, Charged particle tracks and their structure, in Advances in Radiation Chemistry, eds. M. Burton and J. L. Magee, Vol. I, pp. 1 - 102, Wiley-Interscience, New York, 1969.Google Scholar
- 9.A. Chatterjee and W.R. Holley, Energetic electron tracks and DNA strand breaks, Nucl. Tracks Radiat. Meas. 16, #2/3, 127–133 (1989).Google Scholar
- 10.C. Von Sonntag, U. Hagen, A. Schon-Bopp, and D. Schulte-Frohlinde, Radiation-induced strand breaks in DNA: chemical and enzymatic analysis of end groups and mechanistic aspects, Adv. Radiat. Biol. 9, 109–142 (1981).Google Scholar
- 15.M. V. Smoluchowski, Drei Vortrage uber diffusion, brownsche molekular-bewegung und koagulation von kolloidteilchen, Physik Zeitschr., 17, 557 (1916).Google Scholar
- 16.B. Rydberg, Clusters of DNA damage induced by ionizing radiation: formation of kb-sized DNA fragments, submitted to Int. J. of Radiat. Biol.Google Scholar