STRATEGIES OF DNA DAMAGE AND REPAIR
Damage by free radicals to nucleic acids is indicated as a major cause of aging and cancers in humans. Our group has published detailed investigations into the chemical changes in DNA caused by free-radical damage by examining reactions of the purine moieties with HO• radicals producing purine 5’,8-cyclo-2’-deoxynucleosides. These studies into the kinetic mechanisms of DNA lesions, as well as analytical methods to measure DNA damage, have established our group as leading experts in this field. The tandem lesions exist in two diastereoisomeric forms (R and S), with different research groups at international level studying the significance of each lesion type in diseases and aging.
Our research focuses on the relevance of purine 5’,8-cyclo-2’-deoxynucleoside lesions as a whole, even to identifying the various DNA sequences containing the lesion, the biological consequences, as well as enzymatic recognition and repair systems.
The group is active in the following areas:
Biological features of these lesions and enzymatic recognition systems;
Effects of antioxidants or nutrition on the extent and type of DNA lesions;
Reactivity of hydroxyl radicals (HO•) towards oligonucleotide sequences rich in guanine like GpC islands, G-rich introns and G-quadruplex;
Evaluation of the importance of these lesionsin in vivo models, connected with enzymatic-defective syndromes (NER deficiency) including also the comparison with other well-known lesions (8-oxo-purines);
Oligonucleotides containing a purine 5’,8-cyclo-2’-deoxynucleoside lesion according to specific models of interest in diseases, with their chemical-physical characterization;
Gene therapeutics, effect of the DNA damage and formation of cyclopurines, diagnostic genome sequencing (partners of ClickGene);
Diagnostic applications, setting-up efficient measurement of this damage in human samples (exosomes, urine, blood) for health applications.
Reviews:
The Two Faces of the Guanyl Radical: Molecular Context and Behavior
Chatgilialoglu, C. Molecules 2021, 26, 3511.
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On the relevance of hydroxyl radical to purine DNA damage
Chatgilialoglu, C.; Ferreri, C.; Krokidis, M.G.; Masi, A.; Terzidis, M.A. Free Radic. Res. 2021, 55, 000–000. Doi: 10.1080/10715762.2021.18768
5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance
Chatgilialoglu, C.; Ferreri, C.; Geacintov, N.E.; Krokidis, M.G.; Liu, Y.; Masi, A.; Shafirovich, V.; Terzidis, M.A.; Tsegay, P. S. Cells 2019, 8, 513.
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Letter to the Editor:
Cyclopurine (cPu) Lesions: What, How and Why?
Chatgilialoglu, C. Free Radic. Res. 2019, in press.
Recent Publications:
Oxygen-Dependent Accumulation of Purine DNA Lesions in Cockayne Syndrome Cells
Krokidis, M.G.; D’Errico, M.; Pascucci, B.; Parlanti, E.; Masi, A.; Ferreri, C.; Chatgilialoglu, C. Cells 2020, 9, 1671. (Correction: Cells 2021, 10, 41)
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Increased levels of 5',8-Cyclopurine DNA lesions in inflammatory bowel diseases
Masi, A.; Fortini, P.; Krokidis, M.G.; Romeo, E.F.; Bascietto, C.; De Angelis, P.; Guglielmi, V.; Chatgilialoglu, C. Redox Biology, 2020, 34, 101562.
doi.org/10.1016/j.redox.2020.101562
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Oxygen Dependent Purine Lesions in Double-Stranded Oligodeoxynucleotides: Kinetic and Computational Studies Highlight the Mechanism for 5′,8-Cyclopurine Formation
Chatgilialoglu, C.; Eriksson, L.A.; Krokidis, M.G.; Masi, A.; Wang, S; Zhang, R. J. Am. Chem. Soc. 2020, 142, 5825–5833.
Purine DNA Lesions at Different Oxygen Concentration in DNA Repair-Impaired Human Cells (EUE-siXPA)
Krokidis, M.G.; Parlanti, E.; D’Errico, M.; Pascucci, B.; Pino, A.; Alimonti, A.; Pietraforte, D.; Masi, A.; Ferreri, C.; Chatgilialoglu, C. Cells 2019, 8, 1377.
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New Insights into the Reaction Paths of Hydroxyl Radicals with Purine Moieties in DNA and Double-Stranded Oligodeoxynucleotides
Chatgilialoglu, C.; Krokidis, M.G.; Masi, A.; Barata-Vallejo, S.; Ferreri, C.; Terzidis, M.A.; Szreder, T.; Bobrowski, K. Molecules 2019, 24, 3860.
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