UV-induced damage to DNA: effect of cytosine methylation on pyrimidine dimerization

Lara Martinez-Fernandez (1) , Akos Banyasz (2, 3) , Luciana Esposito (1) , Dimitra Markovitsi (3, 2) , Roberto Improta (1)

1 CNR – Istituto di Biostrutture e Bioimmagini
2 DICO - Dynamique et Interactions en phase Condensée
3 LIDyl - Laboratoire Interactions, Dynamiques et Lasers (ex SPAM)

Methylation/demethylation of cytosine plays an important role in epigenetic signaling, the reversibility of epigenetic modifications offering important opportunities for targeted therapies. Actually, methylated sites have been correlated with mutational hotspots detected in skin cancers. The present brief review discusses the physicochemical parameters underlying the specific ultraviolet-induced reactivity of methylated cytosine. It focuses on dimerization reactions giving rise to cyclobutane pyrimidine dimers and pyrimidine (6–4) pyrimidone adducts. According to recent studies, four conformational and electronic factors that are affected by cytosine methylation may control these reactions: the red-shift of the absorption spectrum, the lengthening of the excited state lifetime, changes in the sugar puckering modifying the stacking between reactive pyrimidines and an increase in the rigidity of duplexes favoring excitation energy transfer toward methylated pyrimidines

Domains: Chemical Sciences; Theoretical and/or physical chemistry

Lara Martinez-Fernandez, Akos Banyasz, Luciana Esposito, Dimitra Markovitsi, Roberto Improta. UV-induced damage to DNA: effect of cytosine methylation on pyrimidine dimerization . Signal Transduction and Targeted Therapy, 2017, 2, pp.17021. ⟨10.1038/sigtrans.2017.21⟩. ⟨cea-01571652⟩