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.
Purine 5',8-cyclo-2'-deoxynucleoside lesions in irradiated DNA
Chatgilialoglu, C.; Krokidis, M. G.; Papadopoulos, K.; Terzidis, M. A. Radiat. Phys. Chem. 2016, 128, 75–81.
Purine 5’,8-cyclonucleoside lesions: chemistry and biology
Chatgilialoglu, C.; Ferreri, C.; Terzidis, M. A. Chem. Soc. Rev. 2011, 40, 1368–1382.
Purine 5′,8-cyclo-2′-deoxynucleoside lesions: formation by radical stress and repair in human breast epithelial cancer cells
Krokidis, M. G.; Terzidis, M. A.; Efthimiadou, E.; Zervou, S.; Kordas, G.; Papadopoulos, K.; Hiskia, A.; Kletsas, D.; Chatgilialoglu, C. Free Radic. Res.2017, 51, 470–482.
Radical-induced purine lesion formation is dependent on DNA helical topology
Terzidis, M. A.; Prisecaru, A.; Molphy, Z.; Barron, N.; Randazzo, A.; Dumont, E.; Krokidis, M. G.; Kellett, A.; Chatgilialoglu, C. Free Radic. Res. 2016, 50, S91–S101.
Bypass of a 5’,8-cyclopurine-2’-deoxynucleoside by DNA polymerase b during DNA replication and base excision repair leads to nucleotide misinsertions and DNA strand breaks
Jiang, Z.; Xu, M; Lai, Y; Laverde, E.E.; Terzidis, M.A.; Masi, A; Chatgilialoglu, C; Liu, Y. DNA Repair 2015, 33, 24–34.