DNA tandem lesion: 5′,8-cyclo-2′-deoxyadenosine. The influence on human health

Abstract

Nucleic acids are the targets for various endogenous and exogenous genotoxic agents, including reactive oxygen species. The appearance of a hydroxyl racial (^•OH), the most harmful molecule, next to an oligonucleotide can lead to two types of DNA damage: strand breaks or nucleobase modifications. Since clustered DNA damage is defined as the presence of two or more lesions in one helix turn, purine 5′,8-cyclo-2′-deoxynucleosides are recognized as tandem lesions: both sugar moieties and base have been modified within one nucleoside/nucleotide. The hydrogen abstraction from the C5′ group of nucleosides/nucleotides by ^•OH, with subsequent C8 C5′ cyclisation results in purine 5′,8-cyclonucleoside formation. Due to its unusual 3D structure and the fact that only one radical hit is needed for purine 5′,8-cyclonucleoside formation their influence on genome stability/integrity and DNA repair processes are subjects of medical interest. In the present work the influence of 5′,8-cyclo-2′-deoxyadenosine on DNA spatial geometry and DNA repair hinder in connection with human health, such as neurological disorders is discussed.