Photolyase is an enzyme that repairs DNA damaged by ultraviolet (UV) light. It works by absorbing visible light, harnessing this energy to restore DNA. This process helps maintain the integrity of an organism’s genetic blueprint.
How Light Damages DNA
Ultraviolet (UV) radiation, a component of sunlight, constantly threatens the DNA of living organisms. When DNA absorbs UV light, particularly UV-B, it can lead to specific types of damage. The most common forms of this damage involve the formation of pyrimidine dimers. These dimers occur when two adjacent pyrimidine bases, such as thymine or cytosine, on the same DNA strand become abnormally linked together.
Two primary types of pyrimidine dimers are cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. CPDs are formed by a covalent bond between the C5 and C6 atoms of adjacent pyrimidines, creating a four-membered ring. The less common 6-4 photoproducts involve a bond between the C6 of one pyrimidine and the C4 of an adjacent one. These abnormal structures distort the DNA helix.
The presence of pyrimidine dimers can have serious consequences for a cell. The distorted DNA structure interferes with DNA replication, the process by which a cell makes copies of its genetic material before dividing. It also hinders transcription, the process of reading DNA to create proteins. If these dimers are not repaired, they can lead to errors during DNA replication, resulting in mutations. Accumulation of such mutations can impair cell function, lead to uncontrolled cell growth, or even cause cell death.
How Photolyase Fixes DNA
This repair mechanism, known as photoreactivation, relies on the enzyme’s ability to absorb visible or UV-A light to fuel its repair activity. The enzyme first recognizes and binds to the damaged DNA.
All photolyases contain a two-electron-reduced flavin adenine dinucleotide (FADH-) as a cofactor. Many photolyases also contain a second light-absorbing molecule, or chromophore, which can be either methenyltetrahydrofolate (MTHF) or 8-hydroxy-7,8-didemethyl-5-deazariboflavin (8-HDF). While FADH- is directly involved in the catalytic process, the second chromophore helps capture light energy and transfer it to the FADH-, enhancing the reaction rate, especially under low-light conditions.
Upon absorbing a photon of light, the FADH- cofactor becomes excited. This energized FADH- then donates an electron to the pyrimidine dimer. The addition of this electron to the dimer breaks the abnormal covalent bonds. As the bonds are cleaved, the pyrimidine bases revert to their original, undamaged state. The electron is then transferred back to the FADH-, regenerating the active enzyme. This direct reversal mechanism restores the DNA without the need to remove and replace damaged segments.
The Presence and Purpose of Photolyase
Photolyase is widely distributed across various forms of life, indicating its ancient evolutionary origins and broad significance in protecting genetic material. This enzyme is found in numerous organisms, including bacteria, fungi, plants, and many animals. For instance, its presence has been observed in fish, amphibians, birds, and certain marsupials. In environments with high UV exposure, such as Antarctic diatoms, photolyase activity is particularly evident, demonstrating its role in adapting to intense solar radiation.
However, photolyase is notably absent in placental mammals, including humans. During evolution, placental mammals lost the ability to repair DNA using this light-dependent mechanism. Instead, these organisms rely on more complex, multi-step DNA repair pathways, such as Nucleotide Excision Repair (NER). NER removes a segment of the damaged DNA strand containing the lesion and then synthesizes a new, correct segment.
The widespread presence of photolyase in diverse life forms highlights its importance as a direct defense against solar radiation. For these organisms, it efficiently counteracts the mutagenic effects of UV light, maintaining genomic stability. Its absence in placental mammals suggests an evolutionary divergence where alternative repair mechanisms became sufficient.