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Radiation damage to DNA in DNA–protein complexes

Authors
Journal
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis
0027-5107
Publisher
Elsevier
Publication Date
Volume
711
Identifiers
DOI: 10.1016/j.mrfmmm.2011.02.003
Keywords
  • Dna–Protein Complex
  • Ionizing Radiation
  • Molecular Structure
Disciplines
  • Biology

Abstract

Abstract The most aggressive product of water radiolysis, the hydroxyl (OH) radical, is responsible for the indirect effect of ionizing radiations on DNA in solution and aerobic conditions. According to radiolytic footprinting experiments, the resulting strand breaks and base modifications are inhomogeneously distributed along the DNA molecule irradiated free or bound to ligands (polyamines, thiols, proteins). A Monte-Carlo based model of simulation of the reaction of OH radicals with the macromolecules, called RADACK, allows calculating the relative probability of damage of each nucleotide of DNA irradiated alone or in complexes with proteins. RADACK calculations require the knowledge of the three dimensional structure of DNA and its complexes (determined by X-ray crystallography, NMR spectroscopy or molecular modeling). The confrontation of the calculated values with the results of the radiolytic footprinting experiments together with molecular modeling calculations show that: (1) the extent and location of the lesions are strongly dependent on the structure of DNA, which in turns is modulated by the base sequence and by the binding of proteins and (2) the regions in contact with the protein can be protected against the attack by the hydroxyl radicals via masking of the binding site and by scavenging of the radicals.

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