UV-Type Repair

Repair of human-cell DNA as observed in our assay after UV (254-nm) irradiation differs from ionizing-type repair in two essential aspects. First, the time involved for maximum incorporation of BrlJra is 18-20 hr. Second, the size of the repaired regions (as determined by sensitivity to 313-nm radiation) appears to be equivalent to about 25 BrlJra residues (100 nucleotides). Gradient profiles for a typical UV experiment with 

FIGURE 5. Results of a BrUra photolysis assay for repair after 200 ergs/mm of 254-nm UV. Note molecular weight shift induced by 3 X 10 ergs/mm of 313-nm radiation, indicative of the extent of repair that has occurred in the BrdUrd-containing medium. 

This curvilinear response to 313-nm radiation in these experiments, contrasted to that seen in y-ray experiments, is an indication of target size for the 313-nm radiation. The number of BrUra residues per repaired region in the y-ray experiments present a small target for 313-nm radiation. Saturation is impossible even at extremely high doses of 313-nm. In the case of UV-type repair, however, saturation is possible due to the extensive excision and BrUra substitution that has occurred in the average repaired region. 

CLASSIFICATION OF DNA-DAMAGING CHEMICAL AGENTS ACCORDING TO THE REPAIR SEQjUENCE INDUCED 

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ICR-170 is an acridine with one nitrogen mustard group. It has been employed as an antitumor agent (Creech et al., 1972). In our repair assay, this agent induced repair events similar although not identical to those induced by jV-acetoxy-AAF (Fig. 10). ICR-170 differed from jV-acetoxy-AAF in that the size of the repaired regions with ICR-170 was smaller (approximately ten BrUra residues) than those with jV-acetoxy-AAF (approximately 25 BrUra residues). Nevertheless, ICR-170 clearly induces UV-type repair in normal cells and, like jV-acetoxy-AAF, defective repair in XP cells (see Section VI). 

Vn. XERODERMA PIGMENTOSUM AND UV-TYPE REPAIR AFTER CHEMICAL DAMAGE TO DNA... 

The results with JV-acetoxy-AAF in XP cells led us to examine the response of XP cells to ICR-170, since UV-type repair was observed in normal cells after treatment with this agent. As expected, XP cells showed defective repair of lesions induced by ICR-170 (Fig. 10). 

Chemical agents that damage DNA can be classified into two major groups on the basis of the type of repair observed after treatment—those that induce ionizing-type repair and those that induce UV-type repair. One agent, 4-NQO, induces repair activity of both types. 

Chemicals that induce UV-type repair in normal cells induce lesions that are essentially irreparable in XP cells. 

This example inspired searches for radiation sensitive mutants in yeast. The way was led by Nakai and Matsumoto (1967) who isolated one mutant, UV which was very sensitive to ultraviolet and a second, Xj sensitive to X-rays. They went one step further than isolation and survival curves by making the double-mutant and showing that like double mutants of recA and uvr A in E. coli it was much more sensitive to UV than either single mutant alone. This was the first demonstration of the existence of more than one type or pathway of DNA repair of UV damage in yeast, and inspired the later work of Game and Cox (1972 1973 1974), Brendel and Haynes (1973) and Louise Prakash (1993) in the genetic analysis of pathways of repair in yeast. This led to the classification of the many mutant loci into epistasis groups, which are defined as those mutants which, when combined in the same strain, are no more UV-sensitive than the most sensitive of the two when alone. 

A number of studies are concerned with the free-radical reactions of typical nucleobase lesions. For example, the cyclobutane-type Thy dimer can be split by one-electron reduction [Heelis et al. 1992 reactions (307) and (308)], a process that is relevant to the repair of this typical UV-damage by the photoreactivating enzyme (photolyase, for a review see Carrell et al. 2001, for the energetics of the complex reaction sequence, see Popovic et al. 2002). At 77 K, the dimer radical anion is sufficiently long-lived to be detectable by EPR (Pezeshk et al. 1996). 

In addition to the repair of the epidermal barrier, petrolatum has been used in other types of dermatological treatments. Petrolatum can affect the transmission of UV light during phototherapy... 

For normal cell growth and proliferation, the DNA must be protected from various types of damage. Such damage, induced, for example, by uv irradiation, can involve the chemical alteration of the DNA and, consequently, deleterious mutation. Cells are able to correct or repair such damage. One of the best-understood mechanisms of repair involves the synthesis of new DNA, which replaces the damaged portion. This is called repair synthesis of DNA. The extent of repair synthesis is very small in comparison with the DNA synthesis accompanying replication of the chromosomes. 

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