Cyclobutane pyrimidine dimer

The ultraviolet portion of radiation from sunlight, especially the high-energy UV-B rays, damages the genetic material by triggering photochemical reactions between the bases of the DNA. About 75% of this damage can be attributed to the so-called CPD type (CPD= cyclobutane-pyrimidine dimers). This type results from the fact that 2 adjacent pyrimine bases (e.g. thymine bases) form an extremely stable cyclic compound under UVB radiation (cyclobutane-pyrimidine dimers).

Furthermore, (non-cyclic) 6-4- pyrimidine-pyrimidone photoproducts (6-4-PP) of the DNA are formed. CPDs and 6-4-PP are formed in a ratio of 10:1, so that the biological significance of CPDs is already numerically predominant.

Although the structure of the DNA is initially only slightly disturbed, CPD damage has a very strong effect on the cell, since the biochemical DNA reactions at these damage sites are stopped abruptly. Unrepaired CPDs and 6-4PPs cause UV "signature mutations", which are characteristic of skin carcinomas.

The chemical repair of CPD damage by the body's own repair systems is complicated by the fact that the cyclobutane rings formed when the thymine bases are linked are very stable and thus difficult to "split". Photolyases, which are not formed by humans themselves, are able to repair these CPD damages.

It has been demonstrated that photolyases in liposomal "packaging" can penetrate the keratinocytes. There a translocation of the photoyase into the cell nucleus takes place. The enzyme now binds to the defective DNA and transforms it in such a way that the defective DNA sequence folds out completely into the active centre of the enzyme. This "folding out" of two defective cyclically connected thymine bases from the DNA double helix causes the defective sequence to directly contact the "catalytic cofactor". This very special DNA repair mechanism is called photoreactivation.

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2. Fortunato AE et al. (2015) Dealing with light: the widespread and multitasking cryptochrome/photolyase family in photosynthetic organisms. J Plant Physiol 172:42-54.
3. Liu Z et al (2015) Dynamics and mechanisms of DNA repair by photolyase. Phys Chem Chem Phys 17:11933-11949.