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cis-syn cyclobutane pyrimidine dimer-containing DNA refers to genomic material containing a specific photochemical lesion where adjacent pyrimidine bases, such as thymine or cytosine, are covalently linked by a cyclobutane ring [Nucleic Acids Res., 2004]. This lesion is primarily induced by ultraviolet B (UVB) radiation and causes significant structural distortion of the DNA double helix, leading to the bending and unwinding of the DNA [ResearchGate, 2015]. These structural changes act as a physical barrier that stalls DNA polymerase and RNA polymerase, thereby blocking essential processes like replication and transcription [MDPI, 2022]. If these dimers are not efficiently removed by the cell's nucleotide excision repair (NER) machinery, they can lead to characteristic C-to-T transition mutations [NIH, 2012]. Such mutations are a primary driver in the development of skin cancers, including basal cell carcinoma and melanoma [NIH, 2006]. Therapeutic interventions, such as the topical application of T4 endonuclease V or photolyase enzymes encapsulated in liposomes, specifically target these lesions to accelerate their repair and reduce cancer risk in susceptible individuals [MDPI, 2022]. Consequently, the quantification of these dimers serves as a critical biomarker for assessing UV-induced skin damage and the efficacy of photoprotective treatments [ACS, 2016].
Therapeutic enzymes such as T4 endonuclease V or photolyase are delivered to the site of damage to recognize the structural distortion caused by the dimer. T4 endonuclease V initiates repair by cleaving the glycosidic bond of the 5' pyrimidine and then the phosphodiester bond, while photolyases use light energy to directly reverse the cyclobutane ring, restoring the original bases [Genelink, 2023; MDPI, 2022].
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