![]() The T–C (6–4) dimer is the most common dimer of this type, but C–C and T–T dimers are also observed after UV irradiation. The 6,4-photoproduct is a non-cyclobutane dipyrimidine photoproduct, which is formed upon covalent linkage between the C-6 position of one pyrimidine and the C-4 position of the 3′ adjacent pyrimidine (see Fig. These CPDs have been termed “dark CPDs” 32a. Due to the long half-life of these reactive molecules, this mechanism adds to CPD formation for hours after UV irradiation, but only in melanin-containing cells. Recently, an additional molecular mechanism for the formation of CPDs was described, consisting of photoexcitation of melanin and formation of peroxynitrite. The formation of CPDs is not a random phenomenon: it is influenced by the sequence and conformational context of the affected DNA sequence. CPDs are observed at all possible dipyrimidine sites, with the thymine–thymine dimer (T–T) being the most common, followed by C–T and T–C dimers. They are generated upon saturation of the 5,6 double bonds and formation of a four-membered cyclobutyl ring (see Fig. For DNA damage, the unwinding and bending of the DNA double helix that results from DNA photoproducts is important for DNA damage recognition and initiation of DNA repair.Ĭyclobutane–pyrimidine dimers (CPDs) are the most common DNA photoproducts formed by UV irradiation of the skin. However, the initial cellular sensor for the induction of damage response pathways has not been clearly identified. ![]() An upregulation of the transcription factor p53 plays a pivotal role in many of these cellular damage response pathways. This explains how UV-induced DNA damage can result in acute effects, such as erythema or immune reactions (see Table 86.1). 86.7).įollowing acute cellular injury, including DNA damage, cells activate damage response pathways, which may result in cell cycle arrest, apoptosis, induction of DNA repair pathways, changes in the expression of cell surface proteins, secretion of cytokines, etc. The two major types of pyrimidine dimers are cyclobutane dimers ( Fig. DNA photoproducts are dimers, formed by covalently binding two adjacent pyrimidines in the same polynucleotide chain. Indeed, DNA is regarded as the chromophore for most of the biologic effects of UVB and UVC, including erythema, tanning, immunosuppression, mutagenesis and carcinogenesis 32. UVC and UVB, but much less so UVA, are capable of exciting the DNA molecule directly and subsequently generating DNA photoproducts 31. Bolognia MD, in Dermatology, 2018 UV Induction of DNA Damageĭifferent wavelengths of UV light induce different types of DNA damage.
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