Reversal of Base Damage Caused by UV Radiation

This chapter considers several examples of the direct reversal of DNA damage, all of which are catalyzed by single polypeptide enzymes. Both cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts [(6-4)PP] constitute quantitatively and qualitatively important sources of base damage following the exposure of cells to UV radiation at wavelengths near the absorption maximum of DNA. The chapter discusses a specific DNA repair mode called enzymatic photoreactivation (EPR), or simply photoreactivation. Enzymes that catalyze EPR of CPD in DNA are referred to as pyrimidine dimer-DNA photolyases (PD-DNA photolyase), pyrimidine dimerdeoxyribodipyrimidine photolyases, or pyrimidine dimerphotoreactivating enzymes. The prefix “pyrimidine dimer” is added to distinguish these enzymes from those that catalyze the repair of (6-4)PP by an essentially identical mechanism. These are called (6-4) photoproduct-DNA photolyases ((6-4)PP-DNA photolyase). The chapter describes distribution, properties, structural studies and mechanism of action of PD-DNA photolyase. It also describes PD-DNA photolyase from other organisms and its therapeutic use for protection against sunlight. Next, it explains mechanism of action and C-terminal region of (6-4)PP-DNA photolyase. In addition, the phylogenetic relationships between PD-DNA photolyases, (6-4)PP-DNA photolyases, and blue-light receptor proteins have been suggested, and the following primary subfamilies of proteins have been defined: (i) PD-DNA photolyase proteins; (ii) plant CRY and plant and animal (6-4)PP-DNA photolyase proteins; and (iii) animal CRY proteins. Other covered topics are repair of thymine dimers by a deoxyribozyme, photoreactivation of RNA, and reversal of spore photoproduct in DNA.