Monte Carlo Approach in Assessing Damage in Higher Order Structures of DNA

  • Aloke Chatterjee
  • James B. Schmidt
  • William R. Holley
Part of the Basic Life Sciences book series (BLSC, volume 63)

Abstract

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.

Keywords

Strand Break Double Strand Break Short Fragment Chromatin Fiber Track Structure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    W. R. Holley, A. Chatterjee, and J. L. Magee, Production of DNA strand breaks by direct effects of heavy charged particles, Radiation Research, 121, 161–168 (1990).PubMedCrossRefGoogle Scholar
  2. 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. 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. 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. 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
  6. 6.
    J. L. Magee and A. Chatterjee, Theory of the chemical effects of high-energy electrons, J. Phys. Chem., 82, 2219–2226 (1978).CrossRefGoogle Scholar
  7. 7.
    S. Arnott and D. W. L. Hukins, Optimized parameters for A-DNA and B-DNA, Biochem. Biophys. Res. Commun., 47, 1504–1509 (1972).PubMedCrossRefGoogle Scholar
  8. 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. 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. 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
  11. 11.
    A. Chatterjee and J. L. Magee, Radiation chemistry of heavy-particle tracks. 2. Fricke dosimeter system, J Phys. Chem., 84, 3537–3543 (1980).CrossRefGoogle Scholar
  12. 12.
    A. Chatterjee and W.R. Holley, Energy deposition mechanisms and biochemical aspects of DNA strand breaks by ionizing radiation, Int. J. of Quant. Chem., Vol. XXXIX, 709–727 (1991)CrossRefGoogle Scholar
  13. 13.
    A. Chatterjee, J. L. Magee, and S. K. Dey, The role of homogeneous reactions in the radiolysis of water, Radiation Research, 96, 1–19 (1983).CrossRefGoogle Scholar
  14. 14.
    F. Hutchinson, Chemical changes induced in DNA by ionizing radiation, Prog. Nucleic Acid Res. Mol. Biol., 32, 115–154 (1985).PubMedCrossRefGoogle Scholar
  15. 15.
    M. V. Smoluchowski, Drei Vortrage uber diffusion, brownsche molekular-bewegung und koagulation von kolloidteilchen, Physik Zeitschr., 17, 557 (1916).Google Scholar
  16. 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

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Aloke Chatterjee
    • 1
  • James B. Schmidt
    • 1
  • William R. Holley
    • 1
  1. 1.Division of Life Sciences, Lawrence Berkeley LaboratoryUniversity of California, BerkeleyBerkeleyUSA

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