Molecular dynamics simulation approach to study UV-induced DNA damage
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Molecular dynamics simulation approach to study UV-induced DNA damage
Research areas: Structural and electronic properties of nucleic acids, 

Keywords: Structural Biology, Molecular Dynamics Simulations, Dna Oxidative Damage

Contact person: Luciana Esposito, luciana.espositocnr.it

Actors: Roberto Improta, roberto.improtacnr.it, Luciana Esposito, luciana.espositocnr.it,

Description:
The study of the interaction of nucleic acids with light is of paramountimportance not only for the general understanding of life functioning andevolution, but also for the implications in diseases such as skin cancer andfor the development of biomarkers and therapeutic tools. The absorption ofultraviolet (UV) radiation can cause different types of damage to nucleicacids. The most frequently induced mutagenic DNA lesions involve the formationof chemical bonds between neighboring pyrimidines, leading mainly to twofamilies of dimers: cyclobutane pyrimidine dimers (CPD) and pyrimidine (6-4)pyrimidone adducts (64PPs) [1]. Not only DNA sequences in single and doublestranded structures can be sensitive to UV radiation, but also G-quadruplex(G4) structures, which have been proven to undergo photoinduced reactions via production of highly reactiveGuanine radical species [2].

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.  



Figures:

Selected papers:

[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.

[5] Conti, I., MartinezFernandez, L., Esposito, L., Hofinger, S., Nenov, A., Garavelli, M., Improta,R. (2017). Multiple electronic and structural factors controlCPD and 6-4 Thymine-Thymine photodimerization in DNA duplex. Chemistry23(60):15177-15188.
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Last modified by Marco Comerci on Friday 04 December 2020, 18:00:52
577 views. Last view on Saturday 11 July 2026, 20:57:06