Pyrimidine dimers are molecular lesion

Molecular lesion

A molecular lesion is damage to the structure of a biological molecule such as DNA, enzymes, or proteins that results in reduction or absence of normal function or, in rare cases, the gain of a new function...

s formed from thymine

Thymine

Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...

 or cytosine

Cytosine

Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...

 bases in DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 via photochemical reactions. Ultraviolet light induces the formation of covalent

Covalent bond

A covalent bond is a form of chemical bonding that is characterized by the sharing of pairs of electrons between atoms. The stable balance of attractive and repulsive forces between atoms when they share electrons is known as covalent bonding....

 linkages by reactions localized on the C=C double bonds. In dsRNA, uracil dimers may also accumulate as a result of UV radiation. Two common UV products are cyclobutane

Cyclobutane

Cyclobutane is an organic compound with the formula 4. Cyclobutane is a colourless gas and commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes...

 pyrimidine dimers (CPDs, including thymine dimers) and 6,4 photoproducts. These premutagenic lesions alter the structure of DNA and consequently inhibit polymerases and arrest replication. Dimers may be repaired by photoreactivation or nucleotide excision repair, but unrepaired dimers are mutagenic. Pyrimidine dimers are the primary cause of melanoma

Melanoma

Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...

s in human beings.

Types of dimers

A cyclobutane

Cyclobutane

Cyclobutane is an organic compound with the formula 4. Cyclobutane is a colourless gas and commercially available as a liquefied gas. Derivatives of cyclobutane are called cyclobutanes...

 pyrimidine dimer (CPD) contains a four membered ring arising from the coupling of the C=C double bonds of pyrimidines. Such dimers interfere with base pairing during DNA replication

DNA replication

DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

, leading to mutations.

6,4-photoproducts, or 6,4 pyrimidine-pyrimidones, occur at one third the frequency of CPDs but are more mutagenic. Spore photoproduct lyase

Spore photoproduct lyase

Spore photoproduct lyase is an enzyme that repairs a particular kind of lesion that arises upon UV-radiation of bacterial DNA. This repair mechanism is one of the reasons for the resilience of certain bacterial spores. The enzyme is radical-SAM dependent...

 provides another enzymatic pathway for repair of thymine photodimers.

Mutagenesis

Translesion polymerase

Polymerase

A polymerase is an enzyme whose central function is associated with polymers of nucleic acids such as RNA and DNA.The primary function of a polymerase is the polymerization of new DNA or RNA against an existing DNA or RNA template in the processes of replication and transcription...

s frequently introduce mutations at pyrimidine dimers, both in prokaryotes (SOS mutagenesis) and in eukaryotes. Although the thymine-thymine CPDs (thymine dimers) are the most frequent lesions caused by UV light, translesion polymerases are biased toward introduction of As, so that TT dimers are often replicated correctly. On the other hand, any C involved in CPDs is prone to be deaminated, inducing a C to T transition.

DNA repair

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

Nucleotide excision repair is a more general mechanism for repair of lesions. This process excises the CPD and synthesizes new DNA to replace the surrounding region in the molecule. Xeroderma pigmentosum

Xeroderma pigmentosum

Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet light is deficient. In extreme cases, all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinomas and other skin...

 is a genetic disease in humans in which the nucleotide excision repair process is lacking, resulting in skin discolouration and multiple tumours on exposure to UV light. Unrepaired pyrimidine dimers in humans may lead to melanoma.