A full understanding of the molecular basis of oxidative lesionsrequires the combination of experimental and theoretical techniques, which caninvestigate both ground- and excited-state conformations. In this context, classicalMD simulations have been used to study ground-states of DNA photoreactivesequences, in order to get insights into the population of conformers presentat the instant when a molecule absorbs UV photons.
We have studied DNA sequences particularly prone to photodimerization,also including C5-methylated cytosines (5mC): C5-methylation is an importantmodification playing a role in epigenetic regulation of gene expression andbeing correlated to about 40% of melanomas. MD simulations have allowed to findthe
Structural factors that favour photodimerization in DNA sequences ofdifferent lengths, containing TCG, T5mCG, and TT, within different moleculararchitectures (single and double stranded DNA) [3-5]. We have recently extendedour study to the analysis of the structural effects of Guanine radical cationson G-quadruplex structures formed by tracts of the human telomeric sequences.
In quest’ambito di ricerca abbiamo studiato sequenzedi DNA, particolarmente suscettibili alla fotodimerizzazione, che includonoanche basi di citosina metilate al C5: la metilazione è un’importante modificache gioca un ruolo nella regolazione epigenetica dell’espressione genica e cheè stata riconosciuta come associata a circa il 40% dei melanomi. La dinamicamolecolare ci ha permesso di evidenziare i fattori strutturali che favorisconola fotodimerizzazione in sequenze di DNA diversa lunghezza, contenenti TCG,T5mCG, TT e presenti in diverse architetture (duplex, singolo filamento) [3-5].Lo studio si è esteso recentemente all’analisi degli effetti strutturali dellaformazione di cationi radicali Guanina su architetture G-quadruplex formate datratti di sequenze G-rich del telomero umano.
[1] Martinez-Fernandez,L., Banyasz, A., Esposito, L., Markovitsi, D., Improta, R. (2017).
UV-induced damage to DNA: effect of cytosine methylation on pyrimidinedimerization. Signal Transduct Target Ther. Jun 9;2:17021.
[2] Martinez-Fernandez,L., Esposito, L., Improta, R. (2020).
Studyingthe excited electronic states of guanine rich DNA quadruplexes by quantummechanical methods: main achievements and perspectives. Photochem. Photobiol.Sci 19(4):436-444.
[3] Banyasz, A., Esposito, L., Douki, T., Perron, M., Lepori, C.,Improta, R., Markovitsi, D. (2016) Effect of C5-Methylation of Cytosine on theUV-Induced Reactivity of Duplex DNA: Conformational and Electronic Factors. JPhys Chem B 120, 4232-42.
[4] Esposito,L., Banyasz, A., Douki, T., Perron, M., Markovitsi, D., Improta, R. (2014).
Effect of C5-Methylation of Cytosine on the Photoreactivity of DNA: AJoint Experimental and Computational Study of TCG Trinucleotides.
J. Am.Chem. Soc. 136, 10838-41.