Structure of a hydroxyl radical induced DNA-protein cross-link involving thymine and tyrosine in nucleohistone.
Hydroxyl radical induced formation of a DNA-protein cross-link involving thymine and tyrosine in nucleohistone is described. Hydroxyl radicals were generated in N2O-saturated aqueous solution by ionizing radiation. Samples of nucleohistone were hydrolyzed with HCl and trimethylsilylated. Analysis of irradiated samples by gas chromatography-mass spectrometry with selected-ion monitoring showed the presence of a thymine-tyrosine cross-link on the basis of typical fragment ions from the previously known mass spectrum of its trimethylsilyl derivative. The yield of this DNA-protein cross-link in nucleohistone was measured at incrementing doses of radiation and found to be a linear function of radiation dose between 14 and 300 Gy (J.kg-1). This yield amounted to 0.003 mumol.J-1. The mechanism of formation of this DNA-protein cross-link is thought to result from H atom abstraction by hydroxyl radicals from the methyl group of thymine followed by the addition of the resultant thymine radical to the carbon 3 position of the tyrosine ring and subsequent oxidation of the adduct radical.
Dizdaroglu
M
M
Center for Chemical Technology, National Institute of Standards and Technology, Gaithersburg, Maryland 20899.
Gajewski
E
E
Reddy
P
P
Margolis
S A
SA
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003432:Cross-Linking Reagents; D004247:DNA; D008401:Gas Chromatography-Mass Spectrometry; D006657:Histones; D006878:Hydroxides; D017665:Hydroxyl Radical; D015394:Molecular Structure; D011506:Proteins; D013941:Thymine; D014443:Tyrosine
D003432:Cross-Linking Reagents; D006657:Histones; D006878:Hydroxides; D011506:Proteins; D017665:Hydroxyl Radical; D014443:Tyrosine; D004247:DNA; D013941:Thymine