How UV Damage Can Be Reversed: Photoreactivation, Base Excision Repair, and More

Ultraviolet (UV) radiation can cause significant damage to DNA, leading to various genetic lesions. However, cells have evolved several mechanisms to repair this damage and maintain genomic stability. Here, we explore the key processes that can reverse UV-induced DNA damage:

Direct Reversal by Photolyase (Photoreactivation)

One of the most efficient ways to repair UV damage is through photoreactivation, which involves the enzyme photolyase. This enzyme directly reverses the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs), two of the most common and harmful DNA lesions caused by UV radiation. Photolyase uses the energy from visible light to break apart these dimers, restoring the original DNA structure.

Base Excision Repair (BER)

Base excision repair (BER) is another mechanism that can remove UV-induced DNA damage. In this process, a DNA glycosylase enzyme recognizes and removes the damaged base, creating an abasic site. An endonuclease then cleaves the DNA backbone at the abasic site, and a DNA polymerase fills in the gap with the correct nucleotide, using the complementary strand as a template. Finally, a DNA ligase seals the remaining nick, completing the repair process.

Nucleotide Excision Repair (NER)

Nucleotide excision repair (NER) is a more complex mechanism that can remove a wide range of DNA lesions, including those caused by UV radiation. NER involves the recognition of the damaged site by a protein complex, followed by the incision of the DNA backbone on both sides of the lesion by endonucleases. This allows the removal of an oligonucleotide containing the damaged base. DNA polymerase then fills in the gap with the correct nucleotides, and a ligase seals the remaining nick.

Other Repair Mechanisms

In addition to these main repair pathways, cells have evolved other mechanisms to deal with UV-induced DNA damage:

• Mutagenic repair or dimer bypass, which allows DNA replication to proceed past unrepaired lesions, albeit with a higher chance of introducing mutations
• Recombinational repair, which uses homologous sequences from sister chromatids or homologous chromosomes to restore the correct DNA sequence
• Cell-cycle checkpoints and apoptosis, which can delay cell division or induce programmed cell death in cells with severe DNA damage

By understanding these various repair mechanisms, researchers can develop strategies to enhance DNA repair and protect cells from the harmful effects of UV radiation, which is particularly important in the context of skin cancer prevention and treatment.