Photochemistry, Photophysics, and Mechanism of Pyrimidine Dimer Repair by Dna Photolyase

Kim, Sang‐Tae; Sancar, Aziz

doi:10.1111/j.1751-1097.1993.tb09232.x

Cited by 149 publications

(94 citation statements)

References 63 publications

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“…A permanent mouse embryonic fibroblast cell line carrying the lacI and cII transgenes as mutation reporters was transfected with genes encoding two different DNA photolyases. DNA photolyases are enzymes that use light harvesting chromophores and energy transfer to photorepair photoproducts in DNA (46). There are photolyases specific for either CPDs or (6-4)PPs (reviewed in Refs.…”

Section: Resultsmentioning

confidence: 99%

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

You

Lee

Yoon

et al. 2001

Journal of Biological Chemistry

256

178

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The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 ؋ 10 ؊5 to 34 ؋ 10 ؊5 (background, 8 -10 ؋ 10 ؊5 ). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 ؋ 10 ؊5 to 28 ؋ 10 ؊5(background, 6 -10 ؋ 10 ؊5 ). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.The UV component of sunlight is responsible for the induction of skin tumors, most notably basal cell and squamous cell carcinomas and probably also melanomas (1, 2). Mutations in the p53 gene have been found in a large percentage of human skin malignancies (3-6). The most frequent p53 mutations in skin tumors are C to T or CC to TT mutations involving dipyrimidine sequences. These are considered characteristic mutational changes that can be ascribed to solar UV irradiation (7).The most abundant UV-induced DNA photoproducts are the cis-syn cyclobutane pyrimidine dimers (CPDs) 1 and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). Both lesions are produced by UVB (280 -320 nm) and UVC (200 -280 nm) irradiation in DNA (8, 9). Most of the mutagenic and carcinogenic action of sunlight has been ascribed to the UVB portion of the solar spectrum (10) with a possible role for UVA (320 -400 nm) in the induction of melanoma (11). The absorption of UVA photons by DNA is rather weak, and it is thought that indirect damaging mechanisms may involve endogenous chromophores as radiation absorbing intermediates (12). These can generate reactive oxygen species, which may then damage DNA. Of all lesions formed in DNA after UVB irradiation, the CPD is considered one of the most important ones based on its relatively high abundance, slow repair, and known mutagenicity (8, 9, 13). However, a strong case can be made that the (6-4)PPs are equally if not more important than the CPDs for inducing mutations. C to T transitions can be induced by both CPDs and (6-4)PPs in mutagenesis studies using site-specific photolesions, and (6-4)PP...

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Section: Resultsmentioning

confidence: 99%

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

You

Lee

Yoon

et al. 2001

Journal of Biological Chemistry

256

178

View full text Add to dashboard Cite

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“…Marine organisms can prevent this damage by passive methods with relatively low energetic costs such as sunscreens and non-enzymatic anti-oxidants (Dunlap et al, 2000), or by active, energetically costly, mechanisms such as antioxidant enzymes, photoreactivation and dark-excision DNA repair (Kim and Sancar, 1993;Malloy et al, 1997;Mitchell and Hartman, 1990). Three important points relevant to Antarctic embryos with very slow metabolism are: (i) the metabolic costs of active UV-R mitigation could result in reduced rates of repair; (ii) the continuously cold Antarctic waters would result in reduced activity of enzymes involved in UV-R mitigation if no cold-adaptation has occurred (Somero, 1995;Marshall, 1997) and; (iii) the low UV-R environment in the past may not have imposed selective pressures to evolve efficient UV-R mitigation strategies.…”

Section: Introductionmentioning

confidence: 99%

DNA photorepair in echinoid embryos: effects of temperature on repair rate in Antarctic and non-Antarctic species

Lamare

Barker

Lesser

et al. 2006

Journal of Experimental Biology

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Over recent geological time the Antarctic marine system has been a relatively low ultraviolet radiation (UV-R) environment because of its polar location, high atmospheric ozone concentrations, and extensive seasonal covering by relatively opaque, and highly reflective, sea ice. Recent increases in ultraviolet-B radiation (280-315·nm) due to stratospheric ozone depletion have highlighted the susceptibility of marine ecosystems to this important abiotic factor (Smith et al., 1992;Karentz, 1994;Smith and Cullen, 1995). The occurrence of the spring ozone hole coincides with the development of embryos of many Antarctic marine invertebrates that may be susceptible to the effects of UV-R because of their small size, lack of a protective tegument, and high rate of cell division (Johnsen and Widder, 2001). Antarctic embryos may be especially vulnerable because they have unique physiological adaptations to survive the cold, food-poor Antarctic waters (cf. Marsh et al., 2001).Our recent observations confirm that Antarctic marine larvae are very sensitive to UV-R (Lesser et al., 2004). Echinoid embryos exposed to ambient UV-R under annual Antarctic sea ice (a low UV-R environment with irradiances р1% of surface irradiances), exhibited significantly higher rates of mortality, abnormal development (Ϸ30-50%), and DNA damage than embryos exposed concurrently but under a UV-R filter. Biological weighting functions for DNA damage and survival To determine if an Antarctic species repairs DNA at rates equivalent to warmer water equivalents, we examined repair of UV-damaged DNA in echinoid embryos and larvae. DNA repair by photoreactivation was compared in three species Sterechinus neumayeri (Antarctica), Evechinus chloroticus (New Zealand) and Diadema setosum (Tropical Australia) spanning a latitudinal gradient from polar (77.86°S) to tropical (19.25°S) environments. We compared rates of photoreactivation as a function of ambient and experimental temperature in all three species, and rates of photoreactivation as a function of embryonic developmental stage in Sterechinus. DNA damage was quantified from cyclobutane pyrimidine dimer (CPD) concentrations and rates of abnormal embryonic development. This study established that in the three species and in three developmental stages of Sterechinus, photoreactivation was the primary means of removing CPDs, was effective in repairing all CPDs in less than 24·h, and promoted significantly higher rates of normal development in UV-exposed embryos. CPD photorepair rate constant (k) in echinoid embryos ranged from 0.33 to 1.25·h -1 , equating to a time to 50% repair of between 0.6 and 2.1·h and time to 90%repair between 3.6 and 13.6·h. We observed that experimental temperature influenced photoreactivation rate. In Diadema plutei, the photoreactivation rate constant increased from k=0.58·h -1 to 1.25·h -1 , with a Q 10 =2.15 between 22°C and 32°C. When compared among the three species across experimental temperatures (-1.9 to 32°C), photoreactivation rates vary with a Q 10 =1.39. Photoreactivati...

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“…Marine organisms counteract the effects of ultraviolet radiation (UV-R) through a number of behavioural and physiological strategies, including negative-phototaxis (Pennington & Emlet 1986;Adams 2003), sunscreens , non-enzymatic antioxidants (Dunlap et al 2000), antioxidant enzymes (Lesser & Farrell 2004), DNA repair (Mitchell & Hartman 1990;Kim & Sancar 1993;Malloy et al 1997), and expression of cellcycle genes (Lesser et al 2001. Despite these mitigating strategies, UV-R can have detrimental influences on the marine environment at all trophic levels (see review by de Mora et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Variation in sunscreen compounds (mycosporine‐like amino acids) for marine species along a gradient of ultraviolet radiation transmission within doubtful sound, New Zealand

Lamare¹,

Lesser²,

Barker³

et al. 2004

New Zealand Journal of Marine and Freshwater Research

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We examined the response of four species of New Zealand marine algae (Ecklonia radiata, Apophlaea lyallii, Rhodymenia spp., Ulva lactuca) and a sea urchin (Evechinus chloroticus) to spatial variation in ultraviolet radiation (UV-R) by examining the concentration of UV-R absorbing compounds known as mycosporine-like amino acids (MAAs). The purpose was to understand how, and the degree to which, local marine species could potentially respond to any future increases in incident UV-R in the New Zealand marine environment. The research was undertaken in Doubtful Sound, where we observed a gradient of water column UV-R transmission along the 40 km length of the fiord. We examined spatial differences in MAAs along the UV-B gradient in the macrophytes and temporal changes in MAAs in sea urchin gonads. Among the algae, thallus MAA concentrations (nmol mg -1 protein) ranged from 12.5 to 87.8 in E. radiata, from 433.1 to 1446.4 in A. lyallii, 12.7 Rhodymenia spp., but were not detected in U. lactuca. For E. chloroticus, gonadal MAA concentrations ranged from 83.9 to 224.3 nmol mg -1 protein spatially, and over the year from 1.85 to 14.12 nmol mg -1 dry weight (DW) depending on site and gametogenic cycle. Laboratory manipulations indicated that concentrations of MAAs in E. chloroticus gonads and eggs are influenced by diet. MAA concentration could be correlated with UV-B intensities in two of the algal species. E. chloroticus MAA concentrations could also be correlated with UV-B transmission, which we concluded was a reflection of the greater ingestion and accumulation of MAArich macrophytes at those sites where higher ambient UV-R induced greater MAA concentrations to occur in the algae. Given this, we suggest that one response of marine species to increases in UV-B would be an increase in the synthesis and/or accumulation of MAAs for photoautotrophs and a dietary accumulation of those MAAs in E. chloroticus, an important herbivore in this system.

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Photochemistry, Photophysics, and Mechanism of Pyrimidine Dimer Repair by Dna Photolyase

Cited by 149 publications

References 63 publications

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

DNA photorepair in echinoid embryos: effects of temperature on repair rate in Antarctic and non-Antarctic species

Variation in sunscreen compounds (mycosporine‐like amino acids) for marine species along a gradient of ultraviolet radiation transmission within doubtful sound, New Zealand

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