Further insight in the photochemistry of DNA: structure of a 2-imidazolone (5-4) pyrimidone adduct derived from the mutagenic pyrimidine (6-4) pyrimidone photolesion by UV irradiation.
Pyrimidine (6-4) pyrimidone photoproducts represent one of the major mutagenic and carcinogenic class of DNA damage produced by UV exposure. At present, besides their conversion to their Dewar valence isomer, (6-4) photoproducts are generally believed to be photostable, and the observed biological properties of Paterno-Büchi-derived photoproducts are, thus far, exclusively attributed to these two types of compounds. Using a model system (2) relevant to DNA photochemistry, we have observed that the 5'-base moiety of the (6-4) thymine dimer 3, under far-UV radiation, is able to undergo a ring contraction leading to a 2-oxoimidazoline, 1. This unprecedented secondary photochemical reaction constitutes the first report of a major photomodification affecting (6-4) photoproducts and strongly questions the biological stability of the (6-4) adducts under UV light with 2-imidazolone (5-4) pyrimidone adducts being possibly another source of endogenous DNA damage.
Thomas
Martial
M
Institut de Chimie des Substances Naturelles, CNRS, 1 Avenue de la Terrasse, 91 190 Gif sur Yvette, France.
Guillaume
Dominique
D
Fourrey
Jean-Louis
JL
Clivio
Pascale
P
D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D007093:Imidazoles / Q000737:chemistry* / Q000302:isolation & purification; D018716:Molecular Mimicry; D009153:Mutagens / Q000737:chemistry* / Q000302:isolation & purification; D010777:Photochemistry; D011743:Pyrimidines / Q000737:chemistry* / Q000302:isolation & purification; D011744:Pyrimidinones / Q000737:chemistry* / Q000302:isolation & purification; D014466:Ultraviolet Rays
D007093:Imidazoles; D009153:Mutagens; D011743:Pyrimidines; D011744:Pyrimidinones; C117197:imidazolone; D004247:DNA