title: Discovery and mutagenicity of a guanidinoformimine lesion as a new intermediate of the oxidative deoxyguanosine degradation pathway.
abstract: Oxidative degradation of DNA is a major mutagenic process. Reactive oxygen species (ROS) produced in the course of oxidative phosphorylation or by exogenous factors are known to attack preferentially deoxyguanosine. The latter decomposes to give mutagenic lesions, which under physiological conditions are efficiently repaired by specialized maintenance systems in the cell. Although many intermediates of the degradation pathway are today well-known, we report in this study the discovery of a new intermediate with an interesting guanidinoformimine structure. The structure elucidation of the new lesion was possible by using HPLC-MS techniques and organic synthesis. Finally we report the mutagenic potential of the new lesion in comparison to the known lesions imidazolone and oxazolone using primer extension and pyrosequencing experiments.
authors.affiliation: Center for Integrated Protein Science at the Department of Chemistry, Ludwig-Maximilians-Universität, Munich, Butenandtstraße 5-13, D-81377 Munich, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stathis
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lischke
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Koch
authors.forename: Christian A
authors.initials: CA
authors.lastname: Deiml
authors.forename: Thomas
authors.initials: T
authors.lastname: Carell
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D019791:Guanidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000737:chemistry
chemical_list: D017382:Reactive Oxygen Species; D003849:Deoxyguanosine; D019791:Guanidine