title: Effects of abasic sites on structural, thermodynamic and kinetic properties of quadruplex structures.
abstract: Abasic sites represent the most frequent lesion in DNA. Since several events generating abasic sites concern guanines, this damage is particularly important in quadruplex forming G-rich sequences, many of which are believed to be involved in several biological roles. However, the effects of abasic sites in sequences forming quadruplexes have been poorly studied. Here, we investigated the effects of abasic site mimics on structural, thermodynamic and kinetic properties of parallel quadruplexes. Investigation concerned five oligodeoxynucleotides based on the sequence d(TGGGGGT), in which all guanines have been replaced, one at a time, by an abasic site mimic (dS). All sequences preserve their ability to form quadruplexes; however, both spectroscopic and kinetic experiments point to sequence-dependent different effects on the structural flexibility and stability. Sequences d(TSGGGGT) and d(TGGGGST) form quite stable quadruplexes; however, for the other sequences, the introduction of the dS in proximity of the 3'-end decreases the stability more considerably than the 5'-end. Noteworthy, sequence d(TGSGGGT) forms a quadruplex where dS does not hamper the stacking between the G-tetrads adjacent to it. These results strongly argue for the central role of apurinic/apyrimidinic site damages and they encourage the production of further studies to better delineate the consequences of their presence in the biological relevant regions of the genome.
authors.affiliation: Dipartimento di Chimica delle Sostanze Naturali, Università degli Studi di Napoli Federico II, Via D. Montesano 49, I-80131 Napoli, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Esposito
authors.forename: Luigi
authors.initials: L
authors.lastname: Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Citarella
authors.forename: Antonella
authors.initials: A
authors.lastname: Virgilio
authors.forename: Luciano
authors.initials: L
authors.lastname: Mayol
authors.forename: Concetta
authors.initials: C
authors.lastname: Giancola
authors.forename: Aldo
authors.initials: A
authors.lastname: Galeone
mesh_terms: D002942:Circular Dichroism; D004249:DNA Damage; D004591:Electrophoresis, Polyacrylamide Gel; D005663:Furans / Q000737:chemistry; D054856:G-Quadruplexes; D007700:Kinetics; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D005663:Furans; D009838:Oligodeoxyribonucleotides