UV-Driven Self-Repair of Cyclobutane Pyrimidine Dimers in RNA

Nucleic acids can be damaged by ultraviolet (UV) irradiation, forming structural photolesions such as cyclobutane-pyrimidine-dimers (CPD). In modern organisms, sophisticated enzymes repair CPD lesions in DNA, but to our knowledge, no RNA-specific enzymes exist for CPD repair. Here, we show for the first time that RNA can protect itself from photole-sions by an intrinsic UV-induced self-repair mechanism. This mechanism, prior to this study, has exclusively been ob-served in DNA and is based on charge transfer from CPD-adjacent bases. In a comparative study, we determined the quantum yields of the self-repair of the CPD-containing RNA sequence, GAU=U to GAUU (0.23%), and DNA sequence, d(GAT=T) to d(GATT) (0.44%), upon 285 nm irradiation via UV / Vis spectroscopy and HPLC analysis. After several hours of irradiation, a maximum conversion yield of 16% for GAU=U and 33% for d(GAT=T) was reached. We examined the dynamics of the intermediate charge transfer (CT) state responsible for the self-repair with ultrafast UV pump – IR probe spectroscopy. In the dinucleotides GA and d(GA), we found comparable quantum yields of the CT state of ~50% and lifetimes on the order of several hundred picoseconds. Charge transfer in RNA strands might lead to reactions cur-rently not considered in RNA photochemistry and may help understanding RNA damage formation and repair in modern organisms and viruses. On the UV-rich surface of the early Earth, these self-stabilizing mechanisms likely affected the se-lection of the earliest nucleotide sequences from which the first organisms may have developed.