Comparison of the mechanisms of DNA damage following photoexcitation and chemiexcitation

Abstract

In this review, we compare the mechanisms and consequences of electronic excitation of DNA via photon absorption or photosensitization, as well as by chemically induced generation of excited states. The absorption of UV radiation by DNA is known to produce cyclobutane pyrimidine dimers (CPDs) and thymine pyrimidone photoproducts. Photosensitizers are known to enable such transformations using UV-A and visible light by generating triplet species able to transfer energy to DNA. Conversely, chemiexcitation of DNA is a process related to the formation of high energy peroxides whose decomposition leads to triplet excited species. In practice, both photoexcitation and chemiexcitation produce reactive excited species able to promote some DNA nucleobases to their excited state. We discuss the effect of epigenetic methylation modifications of DNA and the role of endogenous and exogenous photosensitizers on the formation of DNA photoproducts via triplet-triplet energy transfer as well as oxidative DNA damages. The mechanisms of pathogenic pathway involving the generation of CPDs via chemiexcitation (namely dark CPDs, dCPDs) are discussed and compared with photoexcitation considering their spatiotemporal characteristics. Recognition of the multifaceted noxious effects of UV radiation opens new horizons for the development of effective electronically excited quenchers, thereby providing a crucial step toward mitigating DNA photodamage.