Photolyases are specialized enzymes that repair DNA damage caused by ultraviolet (UV) light. Present across various forms of life, including bacteria, fungi, plants, and many animals, they maintain genetic integrity. Their function, called photoreactivation, directly reverses UV-induced DNA damage, restoring it to its original, undamaged state without removing or replacing segments.
The DNA Damage Photolyases Target
Ultraviolet radiation, particularly from sunlight, can induce harmful changes in DNA. Photolyases primarily target pyrimidine dimers, including cyclobutane pyrimidine dimers (CPDs) and, less commonly, 6-4 photoproducts. CPDs form when two adjacent pyrimidine bases, such as thymine or cytosine, on the same DNA strand become covalently linked, creating a four-membered ring. This dimerization distorts the DNA helix, causing a bulge. Such distortions interfere with fundamental cellular processes like DNA replication and transcription, and if unrepaired, can lead to errors in genetic information and mutations.
The Enzyme’s Molecular Machinery
Photolyase enzymes are flavoproteins, containing a flavin adenine dinucleotide (FAD) cofactor. This FAD exists as FADH-, its catalytically active, fully reduced, negatively charged form. Many photolyases also possess a second, light-harvesting molecule called an antenna chromophore, such as methenyltetrahydrofolate (MTHF) or deazaflavin (8-hydroxy-7,8-didemethyl-5-deazariboflavin). These cofactors are precisely positioned within the enzyme’s structure: the antenna chromophore in a shallow cleft between the enzyme’s two domains, and FADH- in the C-terminal catalytic domain. This arrangement enables their cooperative function in DNA repair.
Light’s Essential Role in Repair
Light is required for photolyase function as it provides the energy for DNA repair. The antenna chromophore, with its high light absorption, initially absorbs photons, often in the blue or UVA spectrum. This absorbed energy is then efficiently transferred to the FADH- cofactor through Förster resonance energy transfer.
Upon receiving this energy, FADH- enters an excited state, becoming an electron donor. From this state, FADH- donates an electron directly to the pyrimidine dimer in the damaged DNA. This electron transfer initiates rapid chemical reactions, including bond cleavages within the dimer, breaking the covalent links. The original, undamaged DNA bases are then restored without being excised. Finally, the electron returns to FADH-, regenerating the enzyme for further repair cycles.
Why This Repair Mechanism Matters
Photolyase-mediated DNA repair is a widespread and efficient mechanism for protecting genetic material from UV radiation. Organisms frequently exposed to sunlight, such as plants, bacteria, fungi, insects, amphibians, and fish, rely on this pathway for survival. This repair system helps prevent mutations that could compromise cellular function or lead to diseases. The ability of photolyases to directly reverse DNA damage contributes to genomic stability in these organisms. While humans and other placental mammals do not possess active photolyase enzymes and instead rely on other repair mechanisms, photolyases in other life forms demonstrate diverse evolutionary strategies for safeguarding DNA against environmental challenges.