Thymine dimers

Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA through photochemical reactions . [1] [2] Ultraviolet light (UV) induces the formation of covalent bonds between consecutive bases along the nucleotide chain in the vicinity of their carbon–carbon double bonds . [3] The dimerization reaction may also involve the pyrimidine bases in dsRNA (dual-thread RNA) – uracil or cytosine. There are two common UV products Cyclobutane pyrimidine dimer (CPD) and the 6–4 photoproduct . These premutagenic lesions alter the structure and possibly base-pairing. 50–100 such reactions per second can occur in a skin cell during exposure to sunlight, but are usually corrected within seconds by photolysis reactivation or nucleotide excision repair . Uncorrected lesions can inhibit the polymerase , cause mis-reading during transcription or replication , or cause replication arrest. Pyrimidine dimers are the primary cause of melanoma in humans.

Thymine dimers
Thymine dimers

Type of dimmer

A cyclobutane pyrimidine dimer (CPD) consists of a four-membered ring that results from the coupling of two double-bonded carbons of each pyrimidine. [4] [5] [6] Such dimers interfere with base pairing during DNA replication , leading to mutations.

A 6–4 photoproduct (6–4 pyrimidine–pyrimidone or 6–4 pyrimidine–pyrimidinone) is an alternative dimer containing a single covalent bond between the carbon at the 6th position of a ring and the carbon at the 4th position of the ring. Next base. [7] This type of conversion occurs at about a third of the frequency of CPD but is more mutagenic. A third type of lesion is a Dewar pyrimidineone, which is formed by the reversible isomerization of the 6–4 photoproduct upon further exposure to light .


Translocation polymerases frequently introduce mutations in pyrimidine dimers, both in prokaryotes (SOS mutagenesis) and eukaryotes. Although thymine–thymine CPDs (thymine dimers) are the most frequent lesions caused by UV light, translocation polymerases are biased towards the introduction of As, so that the TT dimer can often be replicated correctly. On the other hand, any C involved in CPD is prone to deafness, which induces a C to T transition.

DNA repair

Pyrimidine dimers present local conformational changes in DNA structure, which allow recognition of the lesion by repair enzymes. [11] In most organisms (except placental mammals such as humans) they can be repaired by photoreactivation. [12] Photoreactivation is a repair process in which photolyase enzymes directly reverse CPDs through photochemical reactions. Lesions on the DNA strand are recognized by these enzymes, followed by absorption of light wavelengths >300 nm (ie fluorescent and sunlight). This absorption enables photochemical reactions to occur, resulting in the elimination of the pyrimidine dimer, returning it to its original state. [13]

Nucleotide excision repair, sometimes called “dark reactivation”, is a more common mechanism for wound repair. This process excises CPD and synthesizes new DNA to replace the surrounding region in the molecule. Xeroderma pigmentosum is a genetic disease in humans that lacks the nucleotide excision repair process, resulting in discoloration of the skin and multiple tumours when exposed to UV light. In humans, unrepaired pyrimidine dimers can cause melanoma. [14]

Some organisms have other ways to repair:

  • Spore photoproduct lyases are found in spore-forming bacteria. This returns the thymine dimers to their original state. [15]
  • Deoxyribodipyrimidine endonucleosidase is found in bacteriophage T4. It is a base excision repair enzyme specific for a pyrimidine dimer. It is then able to open the AP site.