title: Chemical and structural characterization of interstrand cross-links formed between abasic sites and adenine residues in duplex DNA.
abstract: A new type of interstrand DNA-DNA cross-link between abasic (Ap) sites and 2'-deoxyadenosine (dA) residues was recently reported, but the chemical structure and properties of this lesion were not rigorously established. Here we characterized the nucleoside cross-link remnant released by enzymatic digestion of duplex DNA containing the dA-Ap cross-link. A synthetic standard was prepared for the putative nucleoside cross-link remnant 6 in which the anomeric carbon of the 2-deoxyribose residue was connected to the exocyclic N(6)-amino group of dA. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed that the synthetic material 6: matched the authentic cross-link remnant released by enzymatic digestion of cross-linked DNA. These findings establish the chemical structure of the dA-Ap cross-link released from duplex DNA and may provide methods for the detection of this lesion in cellular DNA. Both the nucleoside cross-link remnant 6: and the cross-link in duplex DNA were quite stable at pH 7 and 37°C, suggesting that the dA-Ap cross-link could be a persistent lesion with the potential to block the action of various DNA processing enzymes.
authors.affiliation: Department of Chemistry, University of Missouri, 125 Chemistry Building, Columbia, MO 65211, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Price
authors.affiliation: Department of Chemistry, University of Missouri, 125 Chemistry Building, Columbia, MO 65211, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Catalano
authors.affiliation: Environmental Toxicology Graduate Program, University of California-Riverside, Riverside, CA 92521-0403, USA.
authors.forename: Shuo
authors.initials: S
authors.lastname: Liu
authors.affiliation: Environmental Toxicology Graduate Program, University of California-Riverside, Riverside, CA 92521-0403, USA Department of Chemistry, University of California-Riverside, Riverside, CA 92521-0403, USA.
authors.forename: Yinsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Chemistry, University of Missouri, 125 Chemistry Building, Columbia, MO 65211, USA Department of Biochemistry, University of Missouri, 125 Chemistry Building, Columbia, MO 65211, USA gatesk@missouri.edu.
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
mesh_terms: D000225:Adenine / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D053719:Tandem Mass Spectrometry
chemical_list: D004247:DNA; D000225:Adenine