Radiolysis of nucleosome core DNA: a modelling approach

Purpose: To calculate the expected pattern of frank strand breaks (FSB) ind uced in the DNA of a nucleosome core particle (NCP) by the attack of radiol ytic OH. radicals and to compare this with the experimental pattern of FSB induced by the in uitro irradiation of chicken NCP. Materials and methods: The structure of NCP was obtained from the PDB datab ank. 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 fr agment or of the NCP-DNA was calculated. The probability of reaction of OH. with each sugar reactive sire was calculated using a Monte-Carlo method-ba sed stochastic model. Results: The accessibility of attack sites in the NCP-DNA and the calculate d probabilities of sugar attack are mainly modulated through masking by his tones, and only slightly through bending. The periodicity of the calculated FSB probabilities is identical to that of the experimental FSB probabiliti es in chicken NCP (period 10.4 +/- 0.1 bp). Conclusions: The good agreement between the calculated and experimental res ults recommends the presented modelling procedure as a tool in predicting t he radiosensitivity of DNA in DNA-ligand complexes of known structure.