thyminedimeerit

Thymine dimer, or thyminedimeerit in Dutch, refers to a covalent linkage formed between two adjacent thymine bases in a DNA strand, most commonly as a cyclobutane pyrimidine dimer (CPD) created by ultraviolet (UV) radiation. The dimer links the 5 and 6 positions of the paired thymines, producing a distortion in the DNA double helix that can block normal base pairing and hinder replication and transcription.

Formation and types: CPDs are the most frequent UV-induced lesions and can involve two thymines (TT) as well as neighboring pyrimidines (TC or CC) within a dinucleotide. A related lesion, the 6-4 photoproduct (6-4PP), forms between a pyrimidine pair with a different covalent arrangement and is typically more distorting but less abundant than CPDs.

Biological consequences: If left unrepaired, thymine dimers impede DNA replication and transcription, increasing the risk of mutations. Error-prone translesion synthesis during replication can introduce base substitutions, contributing to mutagenesis and potentially carcinogenesis, particularly after chronic UV exposure.

Repair mechanisms: Nucleotide excision repair (NER) is the primary repair pathway in humans, recognizing distortions caused by CPDs and 6-4PPs and removing a short DNA segment for replacement. Some organisms possess photolyase enzymes that can reverse CPDs in a light-dependent reaction (photoreactivation). In humans, photoreactivation is not functional, so reliance on NER is essential. Defects in NER cause disorders such as xeroderma pigmentosum, with high sensitivity to UV light.

Significance: Thymine dimers are central to UV-induced DNA damage and skin cancer risk. They are a common target of sunscreen protection strategies and are widely studied to understand DNA repair, mutagenesis, and genome stability.