A thymine dimer represents a specific type of damage to DNA, the molecule that carries our genetic instructions. This damage occurs when two adjacent thymine bases, which are building blocks of DNA, on the same strand become abnormally linked. Ultraviolet (UV) light, particularly from sunlight, is the main environmental factor responsible for creating these connections.
The Formation of Thymine Dimers
The formation of a thymine dimer begins when ultraviolet B (UV-B) radiation from the sun penetrates the skin and reaches DNA. UV-B light carries enough energy to be absorbed by the double bonds within adjacent thymine bases, exciting their electrons.
This excited state leads to a chemical reaction where the two neighboring thymine bases form new covalent bonds with each other. This process creates a stable, four-membered ring structure called a cyclobutane pyrimidine dimer (CPD). Imagine two neighboring beads on a string suddenly fusing together, becoming a single, fused unit that distorts the string’s normal arrangement. This dimerization can occur rapidly.
How Thymine Dimers Disrupt DNA Function
Once formed, a cyclobutane pyrimidine dimer creates a physical bulge or kink in the DNA double helix, distorting its structure. This structural alteration interferes with cellular machinery that interacts with DNA. The distorted shape disrupts the passage of enzymes along the DNA strand, impacting critical processes like replication and transcription.
During DNA replication, the enzyme DNA polymerase, which is responsible for copying DNA, encounters the dimer. This enzyme often stalls at the site of the damage because it cannot accurately read the misaligned bases. Such stalling can halt the replication process, or the polymerase might bypass the dimer by inserting incorrect nucleotides opposite the damaged site, leading to a permanent change in the genetic code, known as a mutation. Similarly, during transcription, RNA polymerase, the enzyme that reads genes to create messenger RNA for protein production, also stalls when it encounters a thymine dimer. This blockage prevents the cell from properly synthesizing proteins from the affected gene.
Cellular Repair of Thymine Dimers
Cells possess mechanisms to counteract DNA damage, with Nucleotide Excision Repair (NER) being the primary pathway in humans for repairing thymine dimers. This process begins with specialized enzymes that constantly scan the DNA for distortions in the helix. Upon detecting the damage, a segment of the DNA strand containing the dimer is cut out by nucleases, creating an oligonucleotide about 27 to 29 nucleotides long that includes the damaged bases.
Following the excision, DNA polymerase fills the resulting gap by synthesizing new DNA, using the complementary strand as a template. Finally, another enzyme called DNA ligase seals the newly synthesized segment into the existing DNA strand. While other organisms like plants and bacteria utilize photoreactivation, a light-activated repair mechanism where an enzyme called photolyase breaks the dimer bonds using visible light, humans do not possess this enzyme. Instead, mammalian cells rely on the NER pathway to repair these UV-induced lesions.
Health Consequences of Unrepaired Damage
If a thymine dimer is not repaired before a cell divides, the replication machinery can misread the damaged site, leading to a mutation in the DNA. The accumulation of such mutations, especially in genes that regulate cell growth and division, can disrupt normal cellular control. This disruption can result in uncontrolled cell proliferation, a characteristic feature of cancer.
Unrepaired thymine dimers are directly linked to the development of various skin cancers. These include basal cell carcinoma, squamous cell carcinoma, and melanoma. Xeroderma Pigmentosum (XP), a rare genetic disorder, is a striking example of this link. XP patients have inherited defects in their Nucleotide Excision Repair system, making them highly susceptible to UV damage and significantly increasing their risk of developing multiple skin cancers.