期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 104, 期 9, 页码 1000-1005出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2010.05.006
关键词
DNA oxidation; DNA-protein crosslink; 8-oxo-7,8-dihydro-2 '-deoxyguanosine; Guanidinohydantoin; Copper; Reactive oxygen species
资金
- University of Cincinnati
This work describes the addition of a lysine derivative to guanine base in a nucleoside, an oligonucleotide, and to a large DNA that occurs via oxidation by copper generated reactive oxygen species. Nucleophiles present during oxidation leads to the formation of adducts. In this work, 2'-deoxyguanosine is oxidized by copper generated reactive oxygen species in the presence of a lysine derivative. N alpha-acetyl-lysine methyl ester. Under these conditions the guanidinohydantoin-lysine adduct is observed in a relative yield of 27% when compared to other guanine oxidation products. MS2 strongly supports that lysine is added to the 5-position during the formation of guanidinohydantoin-lysine. A fourteen-nucleotide DNA duplex was oxidized under similar conditions. Digestion showed formation of the same guanidinohydantoin-lysine nucleoside. The reaction was then examined on a 392-nucleotide DNA substrate. Oxidation in the presence of the lysine ester showed adduct formation as stops in a primer extension assay. Adducts predominately formed at a 5'-GGG at position 415. Six of the seven sites that showed reaction greater than 3-fold above background were guanine sites. We conclude from this study that copper can catalyze the formation of DNA-protein adducts and may form in cells with elevated copper and oxidative stress. (C) 2010 Elsevier Inc. All rights reserved.
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