Ultraviolet (UV) radiation is a form of energy emitted primarily by the sun. UV photons possess enough energy to be absorbed directly by biological molecules within skin cells, triggering chemical reactions, particularly within deoxyribonucleic acid (DNA). DNA acts as the fundamental instruction manual for all cellular function. When UV energy penetrates the skin, it can directly alter the chemical bonds within this genetic material, causing damage that threatens the cell’s long-term health if not corrected.
Understanding the UV Spectrum
Solar radiation that reaches the Earth’s surface is classified into three ultraviolet bands based on wavelength. UVC (100 to 280 nanometers) has the highest energy and is the most potent form of UV radiation. Fortunately, the Earth’s ozone layer completely absorbs all UVC radiation, preventing this highly damaging band from reaching the surface.
The medium-wavelength band, UVB (280 to 315 nanometers), is highly biologically active and responsible for causing sunburn. Although the ozone layer absorbs most UVB, a significant portion still penetrates the Earth’s surface, interacting primarily with the superficial layers of the skin (the epidermis). The third band, UVA (315 to 400 nanometers), has the longest wavelength and accounts for approximately 95% of the UV radiation reaching the ground.
UVA radiation is less energetic than UVB but penetrates much deeper into the skin, reaching the dermis layer. Although UVA was historically considered less harmful, both UVA and UVB cause DNA damage. The difference in energy and penetration depth determines their distinct biological effects on various skin layers.
The Molecular Mechanism of DNA Damage
UV radiation, especially UVB, compromises DNA integrity by inducing a reaction between adjacent pyrimidine bases (cytosine and thymine) on the same DNA strand. When UV photons are absorbed, they create abnormal covalent bonds between these neighboring bases, resulting in structures called photoproducts.
The most common photoproduct is the Cyclobutane Pyrimidine Dimer (CPD), accounting for about 75% of all UV-induced DNA lesions. CPDs form a four-carbon ring structure between the two pyrimidines, creating a slight kink (about a 9° bend) in the DNA helix. This distortion interferes with the accurate reading and copying of the genetic code by cellular enzymes.
The second major type of lesion is the pyrimidine-pyrimidone (6-4) photoproduct, or 6-4PP, which makes up about 25% of the damage. Structurally, 6-4PP involves a profound chemical rearrangement, causing a much greater distortion of the DNA double helix, bending it by approximately 44°. Although less abundant, this severe structural change makes 6-4PPs a potent trigger for cellular damage responses and a significant impediment to DNA replication.
Both CPDs and 6-4PPs represent a physical block on the DNA strand, preventing enzymes responsible for replication and transcription from moving smoothly. This blockage means the cell cannot accurately copy its DNA before dividing, which is the direct source of mutations. While CPDs are more numerous, the highly distorting 6-4PPs are often more rapidly recognized by the cell’s repair machinery.
Cellular Defense: DNA Repair Pathways
Cells counteract UV exposure using sophisticated defense mechanisms, primarily the Nucleotide Excision Repair (NER) pathway. This multi-step process is designed to recognize and remove bulky, helix-distorting lesions created by UV radiation, such as CPDs and 6-4PPs. NER operates through two sub-pathways: Global Genomic NER, which scans the entire genome, and Transcription-Coupled NER, which focuses on genes currently being read.
The process begins with damage recognition, where specialized protein complexes continuously scan the DNA for distortions in the double helix. Once a lesion is detected, a large multi-enzyme complex assembles around the damaged site, preparing to excise the error. This complex includes helicases, which are unwinding enzymes that open the DNA double helix around the lesion.
The next step involves a “dual incision” where two different enzymes, XPF and XPG, act as molecular scissors. XPF cuts on one side of the lesion and XPG cuts on the other side, specifically on the damaged strand. This targeted cutting removes a short segment (typically 24 to 30 nucleotides) of the single DNA strand containing the photoproduct.
After the damaged segment is removed, a DNA polymerase enzyme fills the gap using the complementary strand as a template. Finally, a DNA ligase enzyme seals the newly synthesized patch to the existing DNA strand, completing the repair and restoring the original sequence. This efficient mechanism can remove thousands of UV-induced lesions per cell, maintaining genomic stability.
Consequences of Unrepaired Damage
Despite the efficiency of the NER system, heavy UV exposure can overwhelm the repair machinery, leaving some photoproducts uncorrected. When a cell attempts to replicate DNA with these lesions present, replication enzymes often insert an incorrect base, leading to a permanent change in the genetic code known as a mutation. UV-induced mutations show a specific pattern, most often converting a cytosine to a thymine (C>T) or a CC to a TT, characteristic of damage caused by pyrimidine dimers.
These permanent mutations can have three major outcomes for the cell. If the damage is too severe or the mutation occurs in a gene that regulates cell growth, the cell may activate apoptosis, a self-destruct mechanism. Apoptosis is a protective measure that eliminates dangerous cells before they can proliferate.
If the cell avoids apoptosis and the mutation occurs in a gene controlling cell division, such as a tumor suppressor gene or an oncogene, the cell’s growth signals can become permanently deregulated. Mutations in the p53 tumor suppressor gene, for instance, are frequently observed in sun-exposed skin cancers. The accumulation of such errors leads to uncontrolled cell growth and division, the defining characteristic of cancer. This failure of repair systems directly links unrepaired DNA damage to the development of skin cancers, including melanoma and non-melanoma types.