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

Genetic molecules like DNA and RNA can be damaged by ultraviolet (UV) irradiation, forming structural photolesions, such as cyclobutane-pyrimidine-dimers (CPD). Self-repair of CPDs via charge transfer from adjacent bases is an enzyme-free protective mechanism of nucleic acids against UV sunlight. On the surface of the early Earth, these self-stabilizing mechanisms likely affected the selection of the earliest nucleotide sequences. So far, self-repair has exclusively been ob-served in DNA. Here, we show for the first time that RNA, which is crucial to life on Earth and thought of as a progenitor of DNA, can also promote self-repair via charge transfer from adjacent bases. We determined the quantum yields of the self-repair of the CPD-containing DNA sequence, d(GAT=T) (0.44%), and RNA sequence, GAU=U (0.23%), to d(GATT) and GAUU upon 285 nm irradiation via UV / Vis spectroscopy and HPLC analysis. We studied the dynamics of the intermedi-ate charge transfer (CT) state responsible for the self-repair with ultrafast UV pump – IR probe spectroscopy. In the di-nucleotides GA and d(GA), we found comparable quantum yields of the CT state of ~50% and lifetimes on the order of several hundred picoseconds. Charged radicals in RNA strands might lead to reactions currently not considered in RNA photochemistry and may help to understand RNA damage formation and repair in modern cells.