Fig. 1.

ROS have different origins. ROS can arise following exposure to ionizing radiation or light (IR, UV), drugs and other chemicals such as metals. Enzymes, oxygen metabolism and apoptosis also account for ROS production. Finally, the inflammatory responses involving the immune system and bystander signaling also utilize ROS. When ROS enter the nuclear cell compartment, they interact with DNA creating lesions ranging from base or sugar modifications to abasic sites (represented by red stars) and SSBs. ROS-induced DNA lesions can appear in an isolated or clustered form and they are primarily repaired by two BER subpathways: the short-patch and the long-patch pathways. The short-patch or single-nucleotide pathway is initiated by a DNA glycosylase (hOGG1 or hNTH1) that cleaves and removes the altered base, giving an abasic site. This abasic site is then processed by an endonuclease (APE1) allowing DNA polymerase β to process the next step, catalyzing the elimination of the 5′-sugar phosphate residue and filling the gap with a nucleotide. Finally, the nick is sealed by the ligase III/XRCC1 complex. To simplify, only the branch of the short-pathway utilizing a monofunctional glycosylase is represented. SSBs can be repaired by the long-patch pathway (replacing approximately 2–12 nucleotides). This subpathway is dependant on PCNA and FEN1. It contains many of the same factors as the short-patch pathway but in contrast to the short-patch subpathway, DNA synthesis is thought to be mediated by several DNA polymerases including polymerases β, δ and ε. nt: nucleotide.