Oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine leads to substantial DNA-histone cross-links within nucleosome core particles

8-Oxo-7,8-dihydro-2′-deoxyguanosine(8-oxodGuo) is a common primary product of cellular oxidative DNA damage. 8-OxodGuo is more readily oxidized than 2′-deoxyguanosine (dG); a two-electron oxidation generates a highly reactive intermediate (OGox), which forms covalent adducts with nucleophiles, including OH–, free amines, and the side chains of amino acids such as lysine. We determined here that K3Fe(CN)6 oxidation of 8-oxodGuo in nucleosome core particles (NCPs) produces high yields, quantitative (i.e., 100%) in some cases, of DNA-protein cross-links (DPCs). The efficiency of DPC formation was closely related to 8-oxodGuo base pairing and location within the NCP and was only slightly decreased by adding the DNA-protective polyamine spermine to the system. Using NCPs that contained histone mutants, we determined that DPCs result predominantly from OGox trapping by the N-terminal histone amine. The DPCs were stable under physiological conditions and therefore could have important biological consequences. Fo...