Mechanisms of DNA damage, repair, and mutagenesis

Abstract

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust DNA repair and damage-bypass mechanisms faithfully protect the DNA by either removing or tolerating the damage to ensure an overall survival. Deviations in this fine-tuning are known to destabilize cellular metabolic homeostasis, as exemplified in diverse cancers where disruption or deregulation of DNA repair pathways results in genome instability. Because routinely used biological, physical and chemical agents impact human health, testing their genotoxicity and regulating their use have become important. In this introductory review, we will delineate mechanisms of DNA damage and the counteracting repair/tolerance pathways to provide insights into the molecular basis of genotoxicity in cells that lays the foundation for subsequent articles in this issue.

Photochemistry of 1,3-Dicarbonyl Compounds: DNA Photodamage vs. Photoprotection

“…In fact, UV radiation emanating from the sun, considered an exogenous physical agent, is responsible for skin cancers in humans. [43] Among the different regions of sunlight radiation reaching the Earth surface, the ultraviolet (UV) light is the main deleterious agent for DNA. It is subdivided in UVC (100-290 nm), UVB (290-320 nm) and UVA (320-400 nm).…”

“…Excitation of the endogenous or exogenous photosensitizer can lead to a huge variety of photoproducts arising from processes such as energy transfer, electron transfer or production of reactive oxygen species (ROS) ( Figure 6). [43], [44] Nonetheless, cells are equipped with complex and sophisticated systems such as DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which work altogether to reduce the undesirable consequences of DNA damage.…”

“…[43] In humans, the UV-induced DNA damages are repaired by the excision of the damaged portion, followed by the resynthesis using the undamaged strand as template and final ligation. For instance, BER helps to excise small oxidized bases, strand breaks and abasic sites [4], [44], [45] and NER excises bulky photoproducts (CPDs and 6-4PPs).…”

“…It is wellestablished that an important part of the cancer etiology lies in the accumulation of DNA mutations that lead to aberrant RNA and protein, with widespread deregulation of transcription during oncogenesis. [43], [46], [47] Hence, altogether the repair processes are key to maintaining genetic stability in cells.…”

“…The large amount of data that relates UV skin exposure with skin cancer [42], [43], [48] has raised awareness on the harmful effect of excessive sunlight exposure. Thus, skin cancer preventive strategies are now widespread.…”