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A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiationDNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from > 100 Mbp down to < 0.01 Mbp, is modeled using computer simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach. Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition, along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data.
Document ID
20040131503
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Ponomarev, A. L. (NASA Headquarters Washington, DC United States)
Brenner, D.
Hlatky, L. R.
Sachs, R. K.
Date Acquired
August 22, 2013
Publication Date
June 1, 2000
Publication Information
Publication: Radiation and environmental biophysics
Volume: 39
Issue: 2
ISSN: 0301-634X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: RR-11623
CONTRACT_GRANT: CA-49062
CONTRACT_GRANT: GM 57245
Distribution Limits
Public
Copyright
Other