Why Are Pyrimidine Dimers Dangerous to the Body?

Pyrimidine dimers are a type of damage to DNA, caused by ultraviolet (UV) light. These alterations in DNA structure pose significant risks to human health, from common sources like the sun. This article explores why these changes can lead to serious health problems.

How Sunlight Creates DNA Damage

Ultraviolet (UV) radiation, especially the UV-B spectrum, carries enough energy to induce chemical reactions within DNA. When DNA absorbs this UV light, it can cause adjacent pyrimidine bases on the same strand to form covalent bonds. These pyrimidine bases are thymine (T) and cytosine (C). The most common forms are cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts, often involving two thymine bases or a thymine and a cytosine. This process occurs during activities like sunbathing or using tanning beds, exposing skin cells to UV rays.

Why Dimers Halt DNA’s Work

Pyrimidine dimers introduce a physical distortion within the DNA double helix. This creates a “kink” or “bulge” in the DNA’s structure. This structural change interferes with cellular machinery for genetic information.

During DNA replication, DNA polymerases encounter these distorted regions. The abnormal structure can cause the polymerase to stall, halting replication. Alternatively, the polymerase might insert incorrect bases opposite the dimer, leading to errors in the new DNA strand. Similarly, during gene transcription, RNA polymerase, which reads DNA to create mRNA, can also be impeded or blocked by a pyrimidine dimer. This disruption prevents accurate RNA production, which is necessary for protein synthesis.

The Dangerous Outcomes of Unrepaired DNA

When pyrimidine dimers are not repaired, the errors introduced during DNA replication can become permanent changes in the genetic code. These permanent changes are mutations, and dimers are a major source of types like C to T or CC to TT transitions. If mutations occur in genes regulating cell growth and division, they can lead to uncontrolled cell proliferation.

Extensive or unrepairable DNA damage, including pyrimidine dimers, can trigger programmed cell death (apoptosis). This eliminates severely damaged cells and prevents them from multiplying. However, if mutated cells escape this control, they can contribute to various forms of skin cancer. These include basal cell carcinoma, squamous cell carcinoma, and melanoma, where mutations affect genes like p53 or RAS, disrupting cell cycle control. Unrepaired DNA damage also contributes to premature skin aging and can suppress the immune system.

How the Body Fights Back

Cells have DNA repair systems to counteract damage like pyrimidine dimers. The primary defense against these UV-induced lesions is Nucleotide Excision Repair (NER). This multi-step process removes the damaged DNA segment.

NER begins by recognizing the structural distortion caused by the dimer within the DNA helix. A complex of proteins then excises a short DNA strand segment, typically 24-32 nucleotides long, including the dimer. After removing the damaged segment, DNA polymerase synthesizes new DNA to accurately fill the gap, using the undamaged complementary strand as a template. Finally, DNA ligase seals the new patch into the existing DNA strand, restoring DNA integrity. These repair mechanisms are constantly active, maintaining genome stability.

When Defenses Aren’t Enough

Despite the body’s repair systems, pyrimidine dimers can accumulate. Excessive UV exposure can overwhelm the repair machinery, creating more dimers than the cell can fix. This imbalance leads to a backlog of unrepaired lesions.

Some individuals have genetic predispositions that impair DNA repair capabilities. For instance, genetic conditions can result in less efficient or non-functional repair mechanisms. When repair systems are compromised or overwhelmed, unrepaired pyrimidine dimers persist in the DNA. This persistence increases the likelihood of mutations, leading to cellular dysfunction and a higher risk of developing diseases, particularly skin cancers.

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