Investigating the Biochemical Impact of DNA Damage with Structure-Based Probes: Abasic Sites, Photodimers, Alkylation Adducts, and Oxidative Lesions

DNA sustains a wide variety of damage, such as the formation of abasic sites, pyrimidine dieters, alkylation adducts, or oxidative lesions, upon exposure to UV radiation, alkylating agents, or oxidative conditions. Since these forms of damage may be acutely toxic or mutagenic and potentially carcinogenic, it is of interest to gain insight into how their structures impact biochemical processing of DNA, such as synthesis, transcription, and repair. Lesion-specific molecular probes have been used to study polymerise-mediated translesion DNA synthesis of abasic sites and TT dieters, while other probes have been developed for specifically investigating the alkylation adduct O-6-Bn-G and the oxidative lesion 8-oxo-G. In this review, recent examples of lesion-specific molecular probes are surveyed; their specificities of incorporation opposite target lesions compared to unmodified nucleotides are discussed, and limitations of their applications under physiologically relevant conditions are assessed.