Details

Autor(en) / Beteiligte

• Spotheim-Maurizot, M.
• Davídková, M.

Titel

Radiation damage to DNA in DNA–protein complexes

Ist Teil von

• Mutation research, 2011-06, Vol.711 (1-2), p.41-48

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• RADACK model: studied biomolecules of known molecular structure are located in a water volume where OH radicals are randomly generated. The radicals diffuse and either react with the encountered target atom or escape from the box. The model allows to assess the yields and distributions of radiolytic attack. [Display omitted] ► Radiation-induced lesions are inhomogeneously distributed along DNA. ► The distribution is modulated by DNA sequence and structure. ► DNA radiosensitivity is modified by positively charged molecules or by proteins. ► Our original model RADACK accounts for these observations. 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.