Title: Chemical and structural characterization of interstrand cross-links formed between abasic sites and adenine residues in duplex DNA.
Authors: Price, Nathan E; Catalano, Michael J; Liu, Shuo; Wang, Yinsheng; Gates, Kent S
Published In Nucleic Acids Res, (2015 Apr 20)
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.
PubMed ID: 25779045
MeSH Terms: Adenine/chemistry*; Chromatography, High Pressure Liquid; DNA/chemistry*; Nuclear Magnetic Resonance, Biomolecular; Nucleic Acid Conformation*; Tandem Mass Spectrometry