title: A model of the cell nucleus for DNA damage calculations.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Radiation Biophysics Group, Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE17176, Sweden. hooshang.nikjoo@ki.se
authors.forename: Hooshang
authors.initials: H
authors.lastname: Nikjoo
authors.forename: Peter
authors.initials: P
authors.lastname: Girard
mesh_terms: D000512:Alpha Particles / Q000009:adverse effects; D002467:Cell Nucleus / Q000235:genetics* / Q000528:radiation effects*; D002877:Chromosomes, Human / Q000235:genetics / Q000528:radiation effects; D004249:DNA Damage; D059371:DNA, B-Form / Q000737:chemistry / Q000235:genetics; D015894:Genome, Human / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008958:Models, Molecular; D009010:Monte Carlo Method; D009690:Nucleic Acid Conformation; D017785:Photons / Q000009:adverse effects
chemical_list: D059371:DNA, B-Form