Purine 5′,8-cyclo-2′-deoxynucleoside lesions in irradiated DNA

Having their position gained among the smallest bulky DNA lesions recognized by the nucleotide excision repair (NER) enzyme, purine 5′,8-cyclo-2′-deoxynucleosides (5′,8-cPu) are increasingly attracting the interest in the field of genome integrity in health and diseases. Exclusively generated by one of the most harmful of the reactive oxygen species, the hydroxyl radical, 5′,8-cPu can be utilized also for highly valuable information regarding the oxidative status nearby the area where the genetic information is stored. Herein, we have collected the most recently reported biological studies, focusing on the repair mechanism of these lesions and their biological significance particularly in transcription. The LC-MS/MS quantification protocols that appeared in the literature are discussed in details, along with the reported values for the four 5′,8-cPu produced by in vitro γ-radiolysis experiments with calf thymus DNA. Mechanistic insights in the formation of the purine 5′,8-cyclo-2′-deoxynucleosides and their chemical stability are also given in the light of their potential to be utilized as DNA biomarkers of oxidative stress.