Pyrimidine dimers

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Pyrimidine dimers (cyclobutane dimer) are pairs of thymine and cytosine bases in DNA that arise via photochemical reactions.^[1][2] Ultraviolet light induces the formation of covalent linkages by reactions localized on the C=C double bonds.^[3] Two common UV products are cyclobutane pyrimidine dimer (CPD) and 6,4 photoproduct. These premutagenic lesions alter the structure of DNA and consequently inhibit polymerases and arrest replication. Translesion polymerases introduce coding mutations at these points frequently, both in prokaryotes (SOS mutagenesis) and in eukaryotes. The mutational "hotspots," however, do not correspond to the more vulnerable sites to UV irradiation. Although the TT CPD are the most frequent lesions caused by UV light, the mutational spectrum derived from this source of DNA damage is biased towards the increase in T and A. The reason for this bias is that TT CPDs still can pair with AA and are replicated error free by translesion polymerases. Any C involved in CPDs is prone to be deaminated, inducing a C to T transition.^[4]

Contents 1 Cyclobutane photodimers 2 6,4-Photodimers 3 See also 4 References

[edit] Cyclobutane photodimers

Cyclobutane pyrimidine dimer (CPD) features a four membered ring arising from the coupling of the C=C double bonds of pyrimidines.^[5][6][7] T-T dimers thymine dimers formed in between two thymines are most abundant of CPDs. CPD's are readily repaired by nucleotide excision repair machinery. In most organisms they can also be repaired by photolyases, a light-dependent family of enzymes. Xeroderma pigmentosum is a genetic disease where this damage can't be repaired resulting in skin discolouration and multiple tumours on exposure to UV light.

[edit] 6,4-Photodimers

The "6,4-photoproduct," or 6,4 pyrimidine-pyrimidone, occur at one third the frequency of CPD but are more mutagenic.^[7] Spore photoproduct lyase provides another enzymatic pathway for repair of thymine photodimers.^[8]

[edit] See also

• Nucleotide excision repair
• Thymine dimer
• Tanning activator

[edit] References

1. ^ David S. Goodsell (2001). "The Molecular Perspective: Ultraviolet Light and Pyrimidine Dimers". The Oncologist 6 (3): 298–299. 
2. ^ E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. ASM Press, 1118. ISBN 978-1555813192. 
3. ^ S. E. Whitmore, C. S. Potten, C. A. Chadwick, P. T. Strickland, W. L. Morison (2001). "Effect of photoreactivating light on UV radiation-induced alterations in human skin". Photodermatol. Photoimmunol. Photomed. 17 (5): 213–217. doi:10.1034/j.1600-0781.2001.170502.x. PMID 11555330. 
4. ^ J. H. Choi, A. Besaratinia ,D. H. Lee, C. S. Lee, G. P. Pfeifer (2006). "The role of DNA polymerase iota in UV mutational spectra". Mutat. Res. 599 (1-2): 58–65. 
5. ^ R. B. Setlow (1966). "Cyclobutane-Type Pyrimidine Dimers in Polynucleotides". Science 153 (3734): 379–386. doi:10.1126/science.153.3734.379. 
6. ^ Expert reviews in molecular medicine (2 December 2002). Structure of the major UV-induced photoproducts in DNA.. Cambridge University Press.
7. ^ Christopher Mathews and K.E. Van Holde (1990). Biochemistry, 2nd, Benjamin Cummings Publication, 1168. ISBN 978-0805350159. 
8. ^ Jeffrey M. Buis, Jennifer Cheek, Efthalia Kalliri, and Joan B. Broderick (2006). "Characterization of an Active Spore Photoproduct Lyase, a DNA Repair Enzyme in the Radical S-Adenosylmethionine Superfamily". Journal of Biological Chemistry 281: 25994–26003. doi:10.1074/jbc.M603931200..