pyrimidiinidimeerien

Pyrimidine dimers are covalent linkages formed between adjacent pyrimidine nucleotides in DNA, most often involving thymine or cytosine, as a result of ultraviolet (UV) light exposure. The two main forms are cyclobutane pyrimidine dimers (CPDs), where a cyclobutane ring bonds adjacent pyrimidines, and 6-4 photoproducts (6-4PPs), where the C6 of one pyrimidine bonds to the C4 of the neighboring one. CPDs are more common and cause substantial distortion of the DNA helix; 6-4PPs distort DNA more severely but occur less frequently.

Formation occurs when UV photons are absorbed by pyrimidine bases, promoting electronic excitations that enable covalent bonds to form between neighboring pyrimidines. In human skin cells, UVB radiation is particularly effective at generating these lesions. Pyrimidine dimers stall DNA replication and transcription, and, if not repaired, can lead to mutations, most often C to T transitions at dipyrimidine sequences, contributing to carcinogenesis.

Repair mechanisms: In humans, bulky UV-induced lesions are primarily removed by nucleotide excision repair (NER). This pathway recognizes structural distortions, excises a short DNA segment containing the lesion, and fills the gap. Transcription-coupled repair is a subpathway of NER that prioritizes active genes. Some organisms, notably many bacteria and non-vertebrate eukaryotes, use photoreactivation via photolyase to reverse CPDs in light; vertebrates generally lack functional photolyase.

Clinical relevance: defects in NER cause disorders such as xeroderma pigmentosum, with extreme UV sensitivity and a greatly increased risk of skin cancer. Preventive strategies, including sun protection, target the reduction of pyrimidine dimer formation.