Cyclobutane pyrimidine dimer (CPD) (CPD)

Cyclobutane pyrimidine dimers (CPDs) are the most prevalent type of DNA damage induced by ultraviolet (UV) radiation, specifically UVB and UVC [1]. They form when two adjacent pyrimidine bases (cytosine or thymine) in a DNA strand become covalently linked through a cyclobutane ring, distorting the double helix structure [1, 4]. This distortion interferes with DNA replication and transcription, often leading to characteristic UV-signature mutations such as C to T transitions [1]. If left unrepaired by the cell's endogenous nucleotide excision repair (NER) machinery, CPDs can lead to genomic instability, cell death, or the development of skin cancers such as melanoma and basal cell carcinoma [1, 3]. Therapeutic strategies targeting CPDs involve the topical application of DNA repair enzymes, such as photolyases or T4 endonuclease V, encapsulated in liposomes to penetrate skin cells and actively remove these lesions [2, 3]. These interventions aim to supplement the body's natural repair capacity, particularly in individuals with repair deficiencies like Xeroderma pigmentosum or those with extensive actinic damage [2].

Other names

Pyrimidine dimerThymine dimerUV-induced DNA lesionCis-syn cyclobutane pyrimidine dimer

Drugs targeting CPDs function through direct enzymatic repair; photolyases utilize light energy to monomerize the dimer (photoreactivation), while T4 endonuclease V acts as a glycosylase/AP-lyase to initiate the base excision repair pathway [2, 3].