Pyrimidine dimer

Formation of thymine dimer lesion in DNA. The photon causes two consecutive bases on one strand to bind together, destroying the normal base-pairing double-strand structure in that area.

Pyrimidine dimers represent molecular lesions originating from thymine or cytosine bases within DNA, resulting from photochemical reactions.[1][2] These lesions, commonly linked to direct DNA damage,[3] are induced by ultraviolet light (UV), particularly UVC, result in the formation of covalent bonds between adjacent nitrogenous bases along the nucleotide chain near their carbon–carbon double bonds,[4] the photo-coupled dimers are fluorescent.[5] Such dimerization, which can also occur in double-stranded RNA (dsRNA) involving uracil or cytosine, leads to the creation of cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts. These pre-mutagenic lesions modify the DNA helix structure, resulting in abnormal non-canonical base pairing and, consequently, adjacent thymines or cytosines in DNA will form a cyclobutane ring when joined together and cause a distortion in the DNA. This distortion prevents DNA replication and transcription mechanisms beyond the dimerization site.[6]

While up to 100 such reactions per second may transpire in a skin cell exposed to sunlight resulting in DNA damage, they are typically rectified promptly through DNA repair, such as through photolyase reactivation or nucleotide excision repair, with the latter being prevalent in humans. Conversely, certain bacteria utilize photolyase, powered by sunlight, to repair pyrimidine dimer-induced DNA damage. Unrepaired lesions may lead to erroneous nucleotide incorporation by polymerase machinery. Overwhelming DNA damage can precipitate mutations within an organism's genome, potentially culminating in cancer cell formation.[7] Unrectified lesions may also interfere with polymerase function, induce transcription or replication errors, or halt replication. Notably, pyrimidine dimers contribute to sunburn and melanin production, and are a primary factor in melanoma development in humans.

  1. ^ Goodsell DS (2001). "The molecular perspective: ultraviolet light and pyrimidine dimers". The Oncologist. 6 (3): 298–299. doi:10.1634/theoncologist.6-3-298. PMID 11423677. S2CID 36511461.
  2. ^ Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T, eds. (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 1118. ISBN 978-1-55581-319-2.
  3. ^ Peak MJ, Peak JG (October 1991). Effects of Solar Ultraviolet Photons on Mammalian Cell DNA (PDF). Proceedings of the Symposium. Atlanta, Georgia, USA.
  4. ^ Whitmore SE, Potten CS, Chadwick CA, Strickland PT, Morison WL (October 2001). "Effect of photoreactivating light on UV radiation-induced alterations in human skin". Photodermatology, Photoimmunology & Photomedicine. 17 (5): 213–217. doi:10.1111/j.1600-0781.2001.170502.x. PMID 11555330. S2CID 11529493.
  5. ^ Carroll GT, Dowling RC, Kirschman DL, Masthay MB, Mammana A (2023). "Intrinsic fluorescence of UV-irradiated DNA". Journal of Photochemistry and Photobiology A. 437: 114484. doi:10.1016/j.jphotochem.2022.114484. S2CID 254622477.
  6. ^ Cooper GM (2000). "DNA Repair". The Cell: A Molecular Approach (2nd ed.). Sinauer Associates.
  7. ^ Kemp MG, Sancar A (August 2012). "DNA excision repair: where do all the dimers go?". Cell Cycle. 11 (16): 2997–3002. doi:10.4161/cc.21126. PMC 3442910. PMID 22825251.