Pyrimidine dimer

Pyrimidine dimers are chemical species issued from a photochemical reaction involving two pyrimidine (P) nucleobases (thymine, cytosine, or uracil) through formation of new covalent bonds. The discovery of pyrimidine dimers was initially prompted by the observation that ultraviolet (UV) radiation inactivates cells. Over the years, experimental and theoretical studies, performed mainly on model DNA and RNA systems in solution, shed light on the primary processes underlying their formation. In parallel, such dimers have been detected in living cells and skin, and their impact on biological processes has been extensively characterized.

Four principal classes of pyrimidine dimers have been identified: cyclobutane pyrimidine dimers (CPDs, also noted P<>P), (6–4) pyrimidone photoproducts (64PPs), their Dewar valence isomers, and the spore photoproduct (SP). Dimerization may proceed via a direct mechanism, in which UV radiation is absorbed by the pyrimidines, or via an indirect photosensitized process, requiring the action of other molecules absorbing light.

The formation of a pyrimidine dimer within a double helix disrupts Watson–Crick base pairing and distorts the local structure, compromising the accurate transmission of genetic information. If left unrepaired, such lesions can induce transcriptional and replicative errors, contributing to mutagenesis and carcinogenesis. Pyrimidine dimers play a major role in the development of melanoma.

CPDs can undergo photoreversal, a process that regenerates the original nucleobases. In living cells, repair occurs primarily through photoreactivation involving photolyase enzymes or through a base excision repair mechanism.

Beyond the biological significance of pyrimidine dimers as DNA lesions, reversible pyrimidine dimerization has attracted interest for applications in the fields of material science and nanotechnology.