title: Interstrand cross-linking implies contrasting structural consequences for DNA: insights from molecular dynamics.
abstract: Oxidatively-generated interstrand cross-links rank among the most deleterious DNA lesions. They originate from abasic sites, whose aldehyde group can form a covalent adduct after condensation with the exocyclic amino group of purines, sometimes with remarkably high yields. We use explicit solvent molecular dynamics simulations to unravel the structures and mechanical properties of two DNA sequences containing an interstrand cross-link. Our simulations palliate the absence of experimental structural and stiffness information for such DNA lesions and provide an unprecedented insight into the DNA embedding of lesions that represent a major challenge for DNA replication, transcription and gene regulation by preventing strand separation. Our results based on quantum chemical calculations also suggest that the embedding of the ICL within the duplex can tune the reaction profile, and hence can be responsible for the high difference in yields of formation.
authors.affiliation: Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Ens de Lyon, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France.|Univ Lyon, Ens de Lyon, CNRS UMR 5182, Université Claude Bernard Lyon 1, Laboratoire de Chimie, F69342, Lyon, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bignon
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Dršata
authors.affiliation: Univ Lyon, CNRS, Université Claude Bernard Lyon 1, Ens de Lyon, Institut des Sciences Analytiques, UMR 5280, 5 rue de la Doua, F-69100 Villeurbanne, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morell
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Praha 6, Czech Republic.|Laboratory of Informatics and Chemistry, University of Chemistry and Technology Prague, Technická 5, 166 28 Praha 6, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Lankaš
authors.affiliation: Univ Lyon, Ens de Lyon, CNRS UMR 5182, Université Claude Bernard Lyon 1, Laboratoire de Chimie, F69342, Lyon, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Dumont
mesh_terms: D000465:Algorithms; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA