Radiolysis of nucleosome core DNA: a modelling approach.
OBJECTIVE
To calculate the expected pattern of frank strand breaks (FSB) induced in the DNA of a nucleosome core particle (NCP) by the attack of radiolytic OH* radicals and to compare this with the experimental pattern of FSB induced by the in vitro irradiation of chicken NCP.


METHODS
The structure of NCP was obtained from the PDB databank. Using molecular modelling, the structure of a linear DNA fragment with the central 60 bp sequence of NCP-DNA was determined. The accessibility of the sugar attack sites to OH* radicals at each nucleotide of the linear fragment or of the NCP-DNA was calculated. The probability of reaction of OH* with each sugar reactive site was calculated using a Monte-Carlo method-based stochastic model.


RESULTS
The accessibility of attack sites in the NCP-DNA and the calculated probabilities of sugar attack are mainly modulated through masking by histones, and only slightly through bending. The periodicity of the calculated FSB probabilities is identical to that of the experimental FSB probabilities in chicken NCP (period 10.4 +/- 0.1 bp).


CONCLUSIONS
The good agreement between the calculated and experimental results recommends the presented modelling procedure as a tool in predicting the radiosensitivity of DNA in DNA-ligand complexes of known structure.
Begusova
M
M
Nuclear Physics Institute, Radiation Protection Department, Praha, Czech Republic.
Sy
D
D
Charlier
M
M
Spotheim-Maurizot
M
M
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects*; D053938:DNA Fragmentation / Q000528:radiation effects; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry / Q000528:radiation effects*
D009707:Nucleosomes; D004247:DNA