photolyase

Photolyase is a flavoprotein enzyme that repairs UV-induced DNA damage through a light-dependent process called photoreactivation. It directly reverses certain forms of DNA lesions caused by ultraviolet light, most notably cyclobutane pyrimidine dimers (CPDs) and, in some photolyases, 6-4 photoproducts, restoring normal base pairing without removing and resynthesizing DNA.

The enzyme requires two chromophores. A flavin cofactor, typically reduced flavin adenine dinucleotide (FADH−), acts as the catalytic center, while an antenna pigment such as methenyltetrahydrofolate (MTHF) or related molecules captures blue light and transfers energy to FADH−. Upon blue-light absorption, an electron transfer chain is initiated that cleaves the abnormal cyclobutane ring in CPDs or the 6-4 lesion, returning the damaged bases to their correct form. The system then resets to the ground state and becomes ready for another repair cycle.

Photolyases are found in bacteria, fungi, and plants, and in some animals. They are categorized mainly into CPD photolyases and 6-4 photolyases, reflecting their substrate specificity. In many vertebrates, functional photolyase genes are absent or nonfunctional, and related flavoproteins known as cryptochromes regulate circadian rhythms rather than DNA repair.

Physiological role of photolyase is to provide rapid, light-driven repair of UV-induced DNA damage, acting alongside other repair pathways such as nucleotide excision repair. Its activity depends on light availability, so repair efficiency varies with environmental light conditions and organismal physiology.

Applications of photolyase research include studying DNA repair mechanisms and engineering organisms with enhanced UV tolerance for agriculture or industrial microbiology. In humans, therapeutic use remains limited by tissue light exposure and other factors, though related research continues.