Repair of oxidative DNA damage by amino acids

• Published in: Nucleic acids research Vol. 31; no. 21; pp. 6258 - 6263
• Main Authors: Milligan, J. R., Aguilera, J. A., Ly, A., Tran, N. Q., Hoang, O., Ward, J. F.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.11.2003; Oxford Publishing Limited (England)
• Subjects: Amino Acids - chemistry; Amino Acids - metabolism; cystine; DNA Damage - radiation effects; DNA Repair; DNA, Superhelical - chemistry; DNA, Superhelical - metabolism; DNA, Superhelical - radiation effects; Free Radicals - chemistry; Free Radicals - metabolism; Guanine - chemistry; Guanine - metabolism; Kinetics; Oxidants - metabolism; Oxidation-Reduction; Plasmids - chemistry; Plasmids - metabolism; Plasmids - radiation effects; Radiation, Ionizing
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkg816

Guanyl radicals, the product of the removal of a single electron from guanine, are produced in DNA by the direct effect of ionizing radiation. We have produced guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2–, itself derived from the indirect effect of ionizing radiation via thiocyanate scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid DNA with the six most easily oxidized amino acids cysteine, cystine, histidine, methionine, tryptophan and tyrosine and also simple ester and amide derivatives of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine, tyrosine and particularly tryptophan derivatives react to repair guanyl radicals in plasmid DNA with rate constants in the region of ∼105, 105, 106 and 107 dm3 mol–1 s–1, respectively. The implication is that amino acid residues in DNA binding proteins such as histones might be able to repair by an electron transfer reaction the DNA damage produced by the direct effect of ionizing radiation or by other oxidative insults.