Clustered DNA damage

Simple experimental approaches to this problem recently started postulate that the repair of clustered DNA damage leads to conversion of nonlethal lesions, e.g., dihydrothymine, or mutagenic lesions, such as 8-OxoGuanine, into lethal double strand breaks. These early experiments have studied kinetics and influence of excision of base lesion within clustered DNA damage by E. coli and nuclear extracts [27,123-129]. 

David-Cordonnier M-H, Laval J, O Neill P (2000) Clustered DNA damage, influence on damage excision by XRS5 nuclear extracts and Escherichia coli Nth and Fpg proteins. J Biol Chem 275 11866-11873... 

JennerTJ, Fulford J, O Neill P (2001) Contribution of base lesions to radiation-induced clustered DNA damage implication for models of radiation response. Radiat Res 156 590-593 Jeppesen C, Buchardt O, Flenriksen U, Nielsen PE (1988) Photocleavage of DNA photofootprinting of E. coli RNA polymerase bound to promoter DNA by azido-9-acridinylamines. Nucleic Acids Res 16 5755-5770... 

Pearson CG, Shikazono N, Thacker J, O Neill P (2004) Enhanced mutagenic potential of 8-oxo-7,8-di-hydroguanine when present within clustered DNA damage site. Nucleic Acids Res 32 263-270 Phillips TL (1980) Rationale for initial clinical trials and future development of radioprotectors. Cancer Clin Trials 3 165-173... 

Sutherland BM, Bennett PV, Sidorkina O et al. 2000a. Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation. Proc Natl Acad Sci 97 103-108. 

Figure 10. Schematic representation of examples of clustered DNA damage.

DNA acting as a medium to facilitate charge transfer. The distance of charge transfer on the whole is probably limited otherwise the fingerprint of the radiation track, especially at high LET, would be lost and consequently the enhanced radiosensitivity of high LET radiation. The two types of clustered DNA damage discussed are... 

Eccles LJ, Lomax ME, O Neill P. Hierarchy of lesion processing governs the repair, double-strand break formation and mutability of three-lesion clustered DNA damage. Nucleic Acids Res. 2010 38 1123-1134. 

Fujimoto,H.,Pinak,M.,Nemoto,T.,0 Neill,P.,Kume, E., Saito, K., 8c Maekawa, H. (2005). Molecular dynamics simulation of clustered DNA damage sites containing 8-oxoguanine and abasic site. Journal of Computational Chemistry, 26, 788. 

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