Pyrimidine dimers


Pyrimidine dimers
DNA Lesion-Thymine Dimer

Pyrimidine dimers are molecular lesions formed from thymine or cytosine bases in DNA via photochemical reactions.[1][2] Ultraviolet light induces the formation of covalent linkages by reactions localized on the C=C double bonds.[3] In dsRNA, uracil dimers may also accumulate as a result of UV radiation. Two common UV products are cyclobutane pyrimidine dimers (CPDs, including thymine dimers) and 6,4 photoproducts. These premutagenic lesions alter the structure of DNA and consequently inhibit polymerases and arrest replication. Dimers may be repaired by photoreactivation or nucleotide excision repair, but unrepaired dimers are mutagenic. Pyrimidine dimers are the primary cause of melanomas in human beings.

Contents

Types of dimers

Photodimers
Left: Spore photoproduct. Right: Cyclobutane pyrimidine dimer.

A cyclobutane pyrimidine dimer (CPD) contains a four membered ring arising from the coupling of the C=C double bonds of pyrimidines.[4][5][6] Such dimers interfere with base pairing during DNA replication, leading to mutations.

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

Mutagenesis

Translesion polymerases frequently introduce mutations at pyrimidine dimers, both in prokaryotes (SOS mutagenesis) and in eukaryotes. Although the thymine-thymine CPDs (thymine dimers) are the most frequent lesions caused by UV light, translesion polymerases are biased toward introduction of As, so that TT dimers are often replicated correctly. On the other hand, any C involved in CPDs is prone to be deaminated, inducing a C to T transition.[9]

DNA repair

Melanoma-type of skin cancer

Pyrimidine dimers introduce local conformational changes in the DNA structure, which allow recognition of the lesion by repair enzymes.[10] In most organisms (excluding placental mammals such as humans) they can be repaired by photoreactivation.[11] Photoreactivation is a repair process in which photolyase enzymes directly reverse CPDs via photochemical reactions. Lesions on the DNA strand are recognized by these enzymes, followed by the absorption of light wavelengths >300 nm (i.e. fluorescent and sunlight). This absorption enables the photochemical reactions to occur, which results in the elimination of the pyrimidine dimer, returning it to its original state.[12]

Nucleotide excision repair is a more general mechanism for repair of lesions. This process excises the CPD and synthesizes new DNA to replace the surrounding region in the molecule.[12] Xeroderma pigmentosum is a genetic disease in humans in which the nucleotide excision repair process is lacking, resulting in skin discolouration and multiple tumours on exposure to UV light. Unrepaired pyrimidine dimers in humans may lead to melanoma.[13]

References

  1. ^ David S. Goodsell (2001). "The Molecular Perspective: Ultraviolet Light and Pyrimidine Dimers". The Oncologist 6 (3): 298–299. doi:10.1634/theoncologist.6-3-298. PMID 11423677. http://theoncologist.alphamedpress.org/cgi/content/full/6/3/298. 
  2. ^ E. C. Friedberg, G. C. Walker, W. Siede, R. D. Wood, R. A. Schultz and T. Ellenberger (2006). DNA repair and mutagenesis. Washington: ASM Press. p. 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. ^ R. B. Setlow (1966). "Cyclobutane-Type Pyrimidine Dimers in Polynucleotides". Science 153 (3734): 379–386. doi:10.1126/science.153.3734.379. PMID 5328566. 
  5. ^ Expert reviews in molecular medicine (2 December 2002). "Structure of the major UV-induced photoproducts in DNA.". Cambridge University Press. http://www-ermm.cbcu.cam.ac.uk/02005331a.pdf. 
  6. ^ Christopher Mathews and K.E. Van Holde (1990). Biochemistry (2nd ed.). Benjamin Cummings Publication. p. 1168. ISBN 978-0805350159. 
  7. ^ Van Holde, K. E.; Mathews, Christopher K. (1990). Biochemistry. Menlo Park, Calif: Benjamin/Cummings Pub. Co. ISBN 0-8053-5015-2. 
  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 (36): 25994–26003. doi:10.1074/jbc.M603931200. PMID 16829680. 
  9. ^ 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. doi:10.1016/j.mrfmmm.2006.01.003. PMID 16472831. 
  10. ^ Kemmink Johan, Boelens Rolf, Koning Thea M.G., Kaptein Robert, Van , der Morel Gijs A., Van Boom Jacques H. (1987). "Conformational Changes in the oligonucleotide duplex d(GCGTTGCG)*d(GCGAAGCG) induced by formation of a cis-syn thymine dimer". European Journal of Biochemistry 162: 31–43. doi:10.1111/j.1432-1033.1987.tb10538.x. PMID 3028790. 
  11. ^ Essen LO, Klar T (2006). "Light-driven DNA repair by photolyases". Cell Mol Life Sci 63 (11): 1266–77. doi:10.1007/s00018-005-5447-y. PMID 16699813. 
  12. ^ a b Friedberg, Errol C. (23 January 2003) “DNA Damage and Repair”. Nature 421, 436-439. doi:10.1038/nature01408
  13. ^ Vink Arie A., Roza Len (2001). "Biological consequences of cyclobutane pyrimidine dimers". Journal of Photochemistry and Photobiology B: Biology 65 (2–3): 101–104. doi:10.1016/S1011-1344(01)00245-7. 

Wikimedia Foundation. 2010.

Look at other dictionaries:

  • DNA repair — For the journal, see DNA Repair (journal). DNA damage resulting in multiple broken chromosomes DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human… …   Wikipedia

  • Thymine dimer — A thymine dimer is the covalent bonding of two adjacent thymine residues within a DNA molecule, often catalyzed by ultraviolet radiation or chemical mutagenic agents. It is an example of a more general type of DNA damage known as pyrimidine… …   Wikipedia

  • Пиримидиновый димер — DNA Lesion Thymine Dimer Пиримидиновый димер  дефект ДНК, возникающий в результате образования ковалентной связи между двумя соседними пиримидиновыми основаниями (тимидином или цитозином) под действием ультрафиол …   Википедия

  • Direct DNA damage — Direct DNA damage: The UV photon is directly absorbed by the DNA (left). One of the possible reactions from the excited state is the formation of a thymine thymine cyclobutane dimer (right). The direct DNA damage leads to sunburn, causing an… …   Wikipedia

  • Mutagenesis — (pronounced /mjuːtəˈdʒɛnɪsɪs/) is a process by which the genetic information of an organism is changed in a stable manner, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be… …   Wikipedia

  • Xeroderma pigmentosum — XP1 redirects here. For the phone, see Sonim XP1 ToughPhone. Xeroderma pigmentosum Classification and external resources ICD 10 Q82.1 ICD 9 …   Wikipedia

  • Photolyase — is an enzyme that binds complementary DNA strands and breaks certain types of pyrimidine dimers that are caused by exposure to ultraviolet light. Two kinds of pyrimidine dimers arise when a pair of thymine bases or cytosine bases on the same… …   Wikipedia

  • nucleic acid — /nooh klee ik, klay , nyooh /, Biochem. any of a group of long, linear macromolecules, either DNA or various types of RNA, that carry genetic information directing all cellular functions: composed of linked nucleotides. [1890 95; NUCLE(US) + IC;… …   Universalium

  • Melanocyte — and melanin. Latin melanocytus MeSH …   Wikipedia

  • Cyclobutane — Cyclobutane …   Wikipedia