title: From DNA repair to proteome protection: new molecular insights for preventing non-melanoma skin cancers and skin aging.
abstract: Non-melanoma skin cancers (NMSC) are the most common human neoplasms and continue to represent an important public health issue with greater than one million cases diagnosed each year. The primary factor contributing to the molecular pathogenesis of NMSC is unprotected skin exposure to ultraviolet (UV) radiation, ie, UVA (wavelength: 315-400 nm) and UVB rays (wavelength: 280-315 nm) with additional albeit less damaging factors of infrared radiation (wavelength: ~750 nm-1 mm) and environmental pollutants. Skin carcinogenesis by DNA damage is the current predominant paradigm of UV toxicity, which may be caused by direct damaging effects of energy deposited by photons or indirect oxidative action of short-lived reactive oxygen species (ROS) formed from water that reacts with biomacromolecules. UV rays are capable to induce direct both DNA damages, mainly consisting in the formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPDs), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8OHdG). Growing evidence also suggests that the efficiency of DNA repair after exposure to UV radiation is crucially dependent on the levels of oxidative protein damage, including but not limited to DNA repair proteins. Besides DNA lesions, UV-induced oxidative stress can indeed result in carbonylation of proteins, a major form of irreversible protein damage that inactivates their biological function. Interestingly, microorganisms characterized by extreme resistance to UV rays have an intrinsic capacity to protect their proteome, rather than genome, from radiation-induced damage, suggesting that protein carbonylation (PC) may serve as a reliable and innovative biomarker of UV photodamage. This review discusses the main DNA and protein markers of UV-induced damage (eg, CPDs, 8OHdG, and PC) and their relationship and importance to the current understanding of skin carcinogenesis. The identification of key DNA and protein signatures of photodamage may represent a therapeutic target for translational studies of innovative therapeutic and preventive approaches for reducing both skin aging and the morbidity and mortality associated with NMSC.
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: James M
authors.initials: JM
authors.lastname: Spencer
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D018384:Oxidative Stress; D020543:Proteome / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015595:Skin Aging; D012878:Skin Neoplasms / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D020543:Proteome; D017382:Reactive Oxygen Species