Near-UV photolysis of 2-methyl-1,4-naphthoquinone-DNA duplexes: characterization of reversible and stable interstrand cross-links between quinone and adenine moieties.
Near-UV photolysis of 2-methyl-1,4-naphthoquinone (MQ, menadione) tethered DNA induces initial charge transfer followed by either transport of the damage to G or the formation of interstrand cross-links between MQ and DNA bases. In this work, the products responsible for interstrand cross-links have been characterized by mass spectrometry, NMR, and comparison with model compounds. Three major products were formed in the photolysis of MQ-DNA duplexes. Two of the products (isomers) have a cross-link between C2 of a 2,3-saturated MQ moiety and N6 of a dAdo moiety. These products readily convert back to MQ and dAdo upon heating in neutral solution, and thus, they lead to reversible cross-links in MQ-DNA duplexes. The third product has a cross-link between C3 of a 2,3-unsaturated MQ moiety and N6 of an dAdo moiety. This product was stable in neutral solution. The formation of MQ to A cross-links in DNA may be explained by the coupling of MQ radicals that arise from the protonation of MQ radical anions, together with adenin-N6-yl radicals that arise from the deprotonation of A radical cations.
Bergeron
François
F
Group in the Radiation Sciences, Department of Pharmacology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec J1H 4N5, Canada.
Klarskov
Klaus
K
Hunting
Darel J
DJ
Wagner
J Richard
JR
D000225:Adenine / Q000737:chemistry / Q000528:radiation effects*; D016227:Benzoquinones / Q000737:chemistry / Q000528:radiation effects*; D003432:Cross-Linking Reagents / Q000737:chemistry / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage; D010782:Photolysis / Q000528:radiation effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014466:Ultraviolet Rays; D024483:Vitamin K 3 / Q000737:chemistry / Q000528:radiation effects*
D016227:Benzoquinones; D003432:Cross-Linking Reagents; C004532:quinone; D024483:Vitamin K 3; D004247:DNA; D000225:Adenine