title: Diepoxybutane interstrand cross-links induce DNA bending.
abstract: The bifunctional alkylating agent 1,2,3,4-diepoxybutane (DEB) is thought to be a major contributor to the carcinogenicity of 1,3-butadiene, from which it is derived in vivo. DEB forms DNA interstrand cross-links primarily between distal deoxyguanosine residues at the duplex sequence 5'-GNC. In order for the short butanediol tether to span this distance, distortion of the DNA target has been postulated. We determined that the electrophoretic mobility of ligated DNA oligomers containing DEB cross-links was retarded in comparison with control, uncross-linked DNA. Our data are consistent with DNA bending of ∼34° per lesion towards the major groove.
authors.affiliation: Department of Chemistry, Colby College, 5757 Mayflower Hill Drive, Waterville, ME 04901, USA. jtmillar@colby.edu
authors.forename: Julie T
authors.initials: JT
authors.lastname: Millard
authors.forename: Erin E
authors.initials: EE
authors.lastname: McGowan
authors.forename: Sharonda Q
authors.initials: SQ
authors.lastname: Bradley
mesh_terms: D001483:Base Sequence; D002070:Butadienes / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D004852:Epoxy Compounds / Q000737:chemistry*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013237:Stereoisomerism
chemical_list: D002070:Butadienes; D002273:Carcinogens; D003432:Cross-Linking Reagents; D004852:Epoxy Compounds; C007366:diepoxybutane; D004247:DNA; C031763:1,3-butadiene