Ultraviolet (UV) radiation is an invisible energy from sunlight that impacts living organisms. This energy interacts with deoxyribonucleic acid (DNA), the genetic material in cells. Understanding this interaction helps explain its biological effects.
Direct Molecular Alterations
When UV radiation from sunlight penetrates skin cells, it can directly alter the structure of DNA. The primary culprits for these direct changes are the middle wavelengths of UV light, known as UVB radiation. UVB energy is absorbed by the DNA bases, particularly pyrimidines like thymine and cytosine. This absorption leads to specific chemical reactions between adjacent pyrimidine bases on the same DNA strand.
These reactions result in the formation of abnormal molecular structures called photoproducts. The two most common types are cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4 PPs). CPDs are formed when a cyclobutane ring links two neighboring pyrimidines, while 6-4 PPs involve a different covalent bond between the C6 of one pyrimidine and the C4 of an adjacent one. CPDs are the most frequently formed UV-induced DNA lesions, accounting for approximately 75% of these damages, while 6-4 PPs make up about 25%.
The formation of these photoproducts introduces distortions, or “kinks,” into the DNA’s double helix structure. These structural changes interfere with the normal functioning of DNA, hindering processes like replication and transcription, which are essential for cell survival and division.
Biological Outcomes of Damage
When the direct molecular alterations caused by UV radiation are not effectively repaired, they can lead to various biological consequences. The distorted DNA structure can cause errors during DNA replication, resulting in mutations, which are permanent changes in the DNA sequence. A common type of mutation induced by UVB is the conversion of cytosine to thymine (C to T transversion), or even CC to TT double base substitutions. These mutations can disrupt the normal instructions within the cell, potentially activating genes that promote growth or inactivating genes that suppress tumors.
The accumulation of such mutations can lead to uncontrolled cell growth, a hallmark of cancer. Prolonged and unrepaired UV-induced DNA damage is linked to the development of various skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma. 90% of non-melanoma skin cancers and 86% of melanomas are associated with chronic UV exposure.
Beyond cancer, chronic exposure to UV radiation also contributes to premature skin aging, a process known as photoaging. This manifests as visible signs like wrinkles, fine lines, and sunspots. Photoaging is a result of accumulated cellular stress and impaired regeneration, where the persistent DNA damage and subsequent cellular responses contribute to the degradation of collagen and elastin fibers that provide skin structure.
Cellular Defense and Repair
Cells possess mechanisms to counteract the DNA damage induced by ultraviolet radiation. The primary repair pathway responsible for addressing bulky lesions like CPDs and 6-4 PPs is Nucleotide Excision Repair (NER). NER is a system capable of recognizing and removing a wide range of helix-distorting DNA lesions.
The NER process involves a series of coordinated steps. First, specialized proteins detect the presence of the DNA damage, recognizing the structural distortion in the helix. Once the damage is identified, the DNA double helix is unwound around the lesion. Next, a segment of the damaged DNA strand, typically 24-32 nucleotides long, is precisely cut out by enzymes on both sides of the lesion.
Following the excision of the damaged segment, DNA polymerase enzymes synthesize a new, correct DNA sequence to fill the gap, using the undamaged complementary strand as a template. Finally, a DNA ligase enzyme seals the newly synthesized segment into the existing DNA strand, restoring the DNA to its original, functional form.
While NER is efficient, its capacity can be overwhelmed by excessive UV exposure or compromised by genetic defects. When repair mechanisms are defective or insufficient, individuals exhibit extreme sensitivity to UV light and an increased risk of skin cancer due to the accumulation of unrepaired DNA lesions.