Pyrimidine dimers

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We are exposed to UV light whenever we walk into the sun. This UV light makes the chemical changes in the DNA. Within the UV spectrum UV-A (320-400 nm) reaches the earth surface, UV-A is often used in tanning booths. UV-B (295-320 nm) and UV-C (100-295nm) with wavelength of 300 nm and below are blocked by ozone layer. However in the laboratory UV-C is typically used to cause UV damage [1].

Ultraviolet light is absorbed by a double bond thymine and cytosine in DNA, creating covalent bonds between them [2]. The two common UV products are cyclobutane pyrimidine dimer (CPD) and 6, 4 photoproduct. They are premutagenic lesions altering the structure of DNA. If they are not repaired, this lesions inhibit polymerases and arrest replication. But 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 is that TT CPDs still can pair with AA and are error free replicated by translesion polymerases. But any C involved in CPDs is more prone to be deaminated, inducing a C to T transition [5,6].

Cyclobutane Pyrimidine Dimer is a four membered ring structure between 5, 6 double bonds of pyrimidines[3,4]. T-T dimers thymine dimers formed in between two thymine’s are most abundant of CPDs. Cyclobutane Pyrimidine Dimers (also known as cyclobutyl dimer) are repaired within seconds by Nucleotide excision repair machinery. In most organisms they can also be repaired by photolyases, through a light dependent reaction called photoreactivation.

6, 4 Photoproduct or 6, 4 pyrimidine-pyrimidone (6-4) adducts are formed with C-6 of the 5’ pyrimidine and C-4 of the 3’ pyrimidine. The frequency of occurrence of 6, 4 Photoproduct is one third of CPD. 6, 4 Photoproduct is responsible for maximum mutagenicity induced by UV [7].

File:Tddimers.gif File:6,4pp.gif

References

  1. David S. Goodsell, The Molecular Perspective: Ultraviolet Light and Pyrimidine Dimers, The Oncologist, Vol. 6, No. 3, 298-299, June 2001
  2. S. E. Whitmore, C. S. Potten, C. A. Chadwick, P. T. Strickland, W. L. Morison,Effect of photoreactivating light on UV radiation-induced alterations in human skin, Photodermatol Photoimmunol Photomed. 2001 Oct;17(5):213-17
  3. (02)00533-1a.pdf (short code: fig001hah); 2 December 2002, Expert reviews in molecular medicine
  4. Mathews & Vanholde, Biochemistry, 2nd Edition. Benjamin Cummings Publication
  5. Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA and Ellenberger T. DNA repair and mutagenesis. 2006. ASM Press. Washington.
  6. Choi JH, Besaratinia A, Lee DH, Lee CS, Pfeifer GP. The role of DNA polymerase iota in UV mutational spectra.Mutat Res. 2006. 599(1-2):58-65.
  7. Mitchell DL, Nairn RS, The biology of the (6-4) photoproduct. Photochem Photobiol. 1989 Jun;49(6):805-19



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