Probing of DNA Photochemistry with C-Nucleosides of Xanthones and Triphenylene as Photosensitizers To Study the Formation of Cyclobutane Pyrimidine Dimers.

The direct and sequence-dependent investigation of photochemical processes in DNA on the way to cyclobutane pyrimidine dimers (CPDs) as DNA damage requires the probing by photochemically different photosensitizers. The C-nucleosides of xanthone, thioxanthone, 3-methoxyxanthone, and triphenylene as photosensitizers were synthesized by Heck couplings and incorporated into ternary photoactive DNA architectures. This structural approach allows the site-selective excitation of the DNA by UV light. Together with a single defined site for T-T dimerization, not only the direct CPD formation but also the distance-dependent CPD formation in DNA as well as the possibility for energy transport processes could be investigated. Direct CPD formation was observed with xanthone, 3-methoxyxanthone, and triphenylene as sensitizers but not with thioxanthone. Only xanthone was able to induce CPDs remotely by a triplet energy transfer over up to six intervening A-T base pairs. Taken together, more precise information on the sequence dependence of the DNA triplet photochemistry was obtained.

How Far Does Energy Migrate in DNA and Cause Damage? Evidence for Long-Range Photodamage to DNA.

A new DNA architecture addresses the question, how far energy migrates in DNA and forms cyclobutane pyrimidine dimers (CPDs) as photodamages causing skin cancer. The 3-methoxyxanthone nucleoside allows site-selective photoenergy injection into DNA. The designated CPD site lacks the phosphodiester bond and can be placed in defined distances. The CPD formation links two oligonucleotides together and allows probing by gel electrophoresis. We obtained a sigmoidal distance dependence with R0 of 25±3 Å. Below R0 , short-range energy migration occurs with high CPD yields and shallow distance dependence, characteristic for a coherent process. 5-methyl-C as epigenetic modification on the 3'-side facilitates CPD formation. Above R0 , long-range incoherent energy migration occurs over 30 A-T pairs (105.4 Å). The evidence of long-range CPD formation is fundamental for our understanding of DNA photodamaging. Open access funding enabled and organized by Projekt DEAL.