Ultraviolet repair

A variety of mechanisms employing different enzymes repair damaged DNA, as after exposure to chemical mutagens or ultraviolet radiation. 

Ultraviolet Examination. When the surface of many materials is illuminated by ultraviolet light, it emits fluorescence (see Textbox 22). Since no two materials exhibit the same form of fluorescence, the inspection of surfaces under ultraviolet light is often appropriate for determining the nature of the surface differences between an original surface, repaired areas, patches, and repaints are normally clearly shown by differences in fluorescence the technique is not suitable, however, for detecting entire fakes. Objects made of... 

Figure 9.4 Repair of DNA inactivated by ultraviolet light. Light causes die dimerization of adjacent thymine residues that block DNA replication. The four enzymes shown are involved in removal and replacement of a portion of the DNA that contains the dimer.

Defects have been found in these mechanisms that cause various human diseases. For example, patients with the genetic disease xeroderma pigmentosum are especially sensitive to ultraviolet light and develop skin cancer. Skin fibroblasts cultured from these patients have been shown to be defective in DNA repair. 

Stege, H. et al., Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin, Proc. Natl. Acad. Sci. USA 97, 1790-1795, 2000. 

Schwarz, A. et al., Interleukin-12 suppresses ultraviolet radiation-induced apoptosis by inducing DNA repair, Nat. Cell. Biol. 4,26-31, 2002. 

The cyclobutane derivatives can revert to the original bases when irradiated with shorter-wavelength light. This reaction is involved in the repair process, which helps keep damage caused by ultraviolet to a minimum. Some repair mechanisms involve enzymes that are important in the breakdown of cyclobutane dimers by longer-wavelength light. 

Ultraviolet light induces the formation of dimers between adjacent thymines in DNA (also occasionally between other adjacent pyrimidines). The formation of thymine dimers interferes with DNA rephcation and normal gene expression. Thymine dimers are eliminated from DNA by a nucleotide excision-repair mechanism (Figure 1-2-4). 

Importantly, the ERCCl/XPF structure-specific nuclease has an additional role in the repair of cisplatin adducts besides its function in NER the recombinational repair of interstrand crosslinks (19). ERCCl- or XPF-deficient hamster mutant cell lines are hypersensitive to DNA crosslink agents, much more so than to ultraviolet-induced pyrimide dimers, the classical substrates for NER (20,21). Moreover, co-localization of ERCCl foci and RAD51 foci in response to cisplatin treatment has recently been found and may represent recruitment of ERCCl/XPF to sites of recombination repair (22). Previous studies have shown that BRCAl, involved in homologous recombination repair, also plays a major role in the repair of cisplatin DNA damage (23). 

Figure 6.46 Representation of two mechanisms of repair of DNA damage such as ultraviolet light-induced dimerization. The upper line represents cut and patch repair, the lower sister-strand exchange. Thick lines represent newly synthesized DNA. Source From Ref. 12.

As already indicated, the repair processes may inadvertently contribute to errors leading to mutation and more serious endpoints. Some chemicals can affect the repair process, so increasing mutation rates. Lack of a repair system also leads to increased mutations and cancer as occurs in patients suffering from the disease xerodermum pigentosum. These individuals are unable to remove thymidine dimers formed by exposure to ultraviolet light in the DNA of skin cells. They consequently suffer a very high incidence of skin cancer. 

Peak, J.G, Pilas, B., Dudek, E.J. Peak, M.J. (1991) DNA breaks caused by monochromatic 365 nm ultraviolet-A radiation or hydrogen peroxide and their repair in human epithelioid and xeroderma pigmentosum cells. Photochem. Photobiol., 54, 197-203... 

Direct Repair Several types of damage are repaired without removing a base or nucleotide. The best-characterized example is direct photoreactivation of cyclobutane pyrimidine dimers, a reaction promoted by DNA photolyases. Pyrimidine dimers result from an ultraviolet light-induced reaction, and photolyases use energy derived from absorbed light to reverse the dam-... 

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