| Description |
The RNA world hypothesis about the origin of life enjoys wide acceptance. The fact that RNA is capable of catalyzing a wide range of chemical reactions supports a RNA-based primitive metabolism. Redox reactions are very important to metabolism, and at the present time, protein enzymes need the assistance of redox coenzymes such as flavin and nicotinamide to promote these processes. In our current work, we investigate the potential role of 8-oxopurine nucleosides including 8-oxo-7,8-dihydroguanosine (OG) and ribofuranosyl uric acid (RU) as primordial redox coenzymes that could help RNA in redox reactions to support primitive metabolism. More specifically, we propose that 8-oxopurine nucleosides could function as primitive flavins in repairing cyclobutane pyrimidine dimers (CPD) that are photodamaged lesions of nucleic acids and are currently repaired by a flavin-dependent photolyase enzyme. In support of this, we incorporated OG proximal to a CPD in double-stranded oligonucleotides and investigated the repair of the CPD when OG is selectively photoexcited. Our results showed that OG is able to mediate the CPD repair following a flavin-type mechansim. The repair efficiency is dependent upon base pair context as well as the 5' vs. 3' orientation and the strand location. The photorepair activity of OG can operate on versatile environments including directly stacking on to a CPD in the same strand and base pairing with one or the other bases of these lesions. |
