A model of the cell nucleus for DNA damage calculations
- 14 November 2011
- journal article
- research article
- Published by Taylor & Francis Ltd in International Journal of Radiation Biology
- Vol. 88 (1-2), 87-97
- https://doi.org/10.3109/09553002.2011.640860
Abstract
Aims: Development of a computer model of genomic deoxyribonucleic acid (DNA) in the human cell nucleus for DNA damage and repair calculations. The model comprises the human genomic DNA, chromosomal domains, and loops attached to factories. Material and methods: A model of canonical B-DNA was used to build the nucleosomes and the 30-nanometer solenoidal chromatin. In turn the chromatin was used to form the loops of factories in chromosome domains. The entire human genome was placed in a spherical nucleus of 10 micrometers diameter. To test the new target model, tracks of protons and alpha-particles were generated using Monte Carlo track structure codes PITS99 (Positive Ion Track Structure) and KURBUC. Damage sites induced in the genome were located and classified according to type and complexity. Results: The three-dimensional structure of the genome starting with a canonical B-DNA model, nucleosomes, and chromatin loops in chromosomal domains are presented. The model was used to obtain frequencies of DNA damage induced by protons and alpha-particles by direct energy deposition, including single- and double-strand breaks, base damage, and clustered lesions. Conclusions: This three-dimensional model of the genome is the first such model using the full human genome for the next generation of more comprehensive modelling of DNA damage and repair. The model combines simple geometrical structures at the level of domains and factories with potentially full detail at the level of atoms in particular genes, allowing damage patterns in the latter to be simulated.Keywords
This publication has 30 references indexed in Scilit:
- Effect of Linear Energy Transfer (LET) on the Complexity of α-Particle-Induced Chromosome Aberrations in Human CD34+CellsRadiation Research, 2007
- Accurate Electron Inelastic Cross Sections and Stopping Powers for Liquid Water over the 0.1-10 keV Range Based on an Improved Dielectric Description of the Bethe SurfaceRadiation Research, 2007
- A Complete Dielectric Response Model for Liquid Water: A Solution of the Bethe Ridge ProblemRadiation Research, 2005
- Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase RosettesPLoS Biology, 2005
- The Effect of Model Approximations on Single-Collision Distributions of Low-Energy Electrons in Liquid WaterRadiation Research, 2005
- Predicting three-dimensional genome structure from transcriptional activityNature Genetics, 2002
- Visualizing Chromatin Dynamics in Interphase NucleiScience, 2002
- Simulation of Exon Deletion Mutations Induced by Low-LET Radiation at theHPRTLocusRadiation Research, 2001
- Monte Carlo Simulation of the Production of Short DNA Fragments by Low-Linear Energy Transfer Radiation Using Higher-Order DNA ModelsRadiation Research, 1998
- Calculation of Initial Yields of Single- and Double-strand Breaks in Cell Nuclei from Electrons, Protons and Alpha ParticlesInternational Journal of Radiation Biology, 1989