DNA Damage: Introduction
DNA in living organisms is permanantly subjected to a plethora of DNA-damaging agents leading to aberrant DNA structures, thereby impacting genomic stability and, consequently, health and disease states. According to Chakarov et al. (2014), DNA damage can be considered as “Any modification in the physical and/or chemical structure of DNA resulting in an altered DNA molecule which is different from the original DNA molecule with regard to its physical, chemical and/or structural properties” 1. Due to the origin of its factors, DNA damage can be classified into two classes, endogenous and exogenous. Exogenous DNA damage develops after the exposure of DNA to environmental agents, including genotoxic/cytotoxic chemicals and physical factors such as extrinsically inflicted UV and ionizing radiation, driving the frequency of DNA single (SSB) and double strand breaks (DSB). The bulk of endogenous DNA lesions results from potentially aggressive agents produced by normal cell metabolism such as reactive oxygen (ROS) and nitrogen species (RNS) generated by respiration and lipid peroxidation as well as spontaneous hydrolysis of nucleotide residues. However, exogenous and endogenous DNA-damaging factors can modify divers cellular functions including respiration, mitochondrial biogenesis and oxidative/nitrosative stress via expanded creation of ROS and RNS and thus affect cellular physiology. Since unresolved or inadequately repaired DNA damages are implicated in diverse human diseases and cancers, powerful DNA damage tolerance and repair mechanisms assist the cell to tolerate or eliminate the lesions and thus favoring survival.