Photosensitized reactions of nucleic acids

Cadet, Jean; Berger, M.; Decarroz, C.; Wagner, J. Richard; Lier, Johan E. van; Ginot, Y.M.; Vigny, Paul

doi:10.1016/s0300-9084(86)80097-9

Cited by 177 publications

(79 citation statements)

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“…Some of these oxidized forms of thymine subsequently react further to form urea. Some of the same types of damage also occurs to DNA during oxidative stress (5,15,16).The damage to the thymine bases in DNA is of special interest because the major forms of damaged thymine are known; thymine is the most easily oxidized base, and many of the biological consequences of damaged thymines are known. Thus, the damaged thymines offer the opportunity to correlate the changes in the physical properties of DNA caused by ionizing radiation or oxidative stress with the biological effects.…”

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Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

Kung

Bolton

1997

Journal of Biological Chemistry

105

114

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Oxidative stress, ionizing radiation, and other events can induce the oxidation of the thymine in DNA to thymine glycol. The presence of thymine glycol can have significant biological consequences, and there are specific repair enzymes for thymine glycol in a wide range of organisms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combined use of NMR and restrained molecular dynamics. The duplex of d(C 1 G 2 C 3 G 4 A 5 Tg 6 A 7 C 8 G 9 C 10 C 11 ) paired with d(G 22 C 21 G 20 -C 19 T 18 A 17 T 16 G 15 C 14 G 13 G 12 ), with Tg indicating thymine glycol, has been used for these studies. The structure shows that the thymine glycol induces a significant, localized structural change with the thymine glycol largely extrahelical. This structural information is consistent with the biological consequences of thymine glycol in DNA. This structure is compared with that of a DNA duplex with an abasic site in the same sequence context.Damage to DNA can occur by the spontaneous deamination of cytosine to uracil and through the action of alkylating agents, oxidants, drugs, and toxins, ionizing radiation, and other modes of action (1-3). The exposure of DNA in cells bound to proteins as a solid or free in solution to ionizing radiation or to oxidative stress can lead to the conversion of thymine to thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine). Approximately 10 -20% of the damage to DNA induced by ionizing radiation, including that used to treat tumors, is the result of thymine base oxidation and fragmentation. These products can also be produced by oxidative stress. In addition, the importance of damaged DNA as a control on the cell cycle is increasingly becoming a focus of research efforts so that the effects of damaged thymines on the structures, stabilities, dynamics, and interactions of DNA are of interest.It has been known for several decades that ionizing radiation can stop the reproduction of cells as well as kill cells. These activities form the basis for using radiation in chemotherapy, and the research in this area has been frequently reviewed (1-13). Since the mid-1950s there have been studies on the effects of ionizing radiation on the chemical integrity of DNA (4,5,7,9, 14). Ionizing radiation can induce a number of types of damage to DNA including single and double strand breaks, oxidation of the purine and pyrimidine bases, and cross-linking of DNA with proteins. Radiation-generated oxidants are thought to react with thymine to lead to the formation of thymine glycol, thymine peroxide, thymine hydroperoxide, and other oxidized forms of the base. Some of these oxidized forms of thymine subsequently react further to form urea. Some of the same types of damage also occurs to DNA during oxidative stress (5,15,16).The damage to the thymine bases in DNA is of special interest because the major forms of damaged thymine are known; thymine is the most easily oxidized base, and many of the biological consequences of damaged thymines a...

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“…Some of these oxidized forms of thymine subsequently react further to form urea. Some of the same types of damage also occurs to DNA during oxidative stress (5,15,16).…”

mentioning

confidence: 99%

Structure of a Duplex DNA Containing a Thymine Glycol Residue in Solution

Kung

Bolton

1997

Journal of Biological Chemistry

105

114

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“…The damage induced by singlet oxygen in bacterial, plasmid, and bacteriophage DNAs is lethal and/or mutagenic (16,17,21,34). Although the only damaged base that has been identified in MB-light-treated DNA is 8-hydroxyguanine (43), the formation of other lesions cannot be excluded (11).…”

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Escherichia coli Fpg protein and UvrABC endonuclease repair DNA damage induced by methylene blue plus visible light in vivo and in vitro

et al. 1991

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pBR322 plasmid DNA was treated with methylene blue plus visible light (MB-light) and tested for transformation efficiency in Escherichia coli mutants defective in either formamidopyrimidine-DNA glycosylase (Fpg protein) and/or UvrABC endonuclease. The survival of pBR322 DNA treated with MB-light was not significantly reduced when transformed into either fpg-1 or uvrA single mutants compared with that in the wild-type strain. In contrast, the survival of MB-light-treated pBR322 DNA was greatly reduced in the fpg-1 uvrA double mutant. The synergistic effect of these two mutations was not observed in transformation experiments using pBR322 DNA treated with methyl methanesulfonate, UV light at 254 nm, or ionizing radiation. In vitro experiments showed that MB-light-treated pBR322 DNA is a substrate for the Fpg protein and UvrABC endonuclease. The number of sites sensitive to cleavage by either Fpg protein or UvrABC endonuclease was 10-fold greater than the number of apurinic-apyrimidinic sites indicated as Nfo protein (endonuclease IV)-sensitive sites. Seven Fpg protein-sensitive sites per pBR322 molecule were required to produce a lethal hit when transformed into the uvrA fpg-1 mutant. These results suggest that MB-light induces DNA base modifications which are lethal and that these modifications are repaired by Fpg protein and UvrABC endonuclease in vivo and in vitro. Therefore, one of the physiological functions of Fpg protein might be to repair DNA base damage induced by photosensitizers and light.The Fpg protein of Escherichia coli was initially identified as a DNA glycosylase which excised the imidazole ringopened form of N7-methylguanine (2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine or Fapy) residues in DNA (2, 9, 13). This enzyme was shown also to liberate the imidazole ring-opened form of adenine residues from DNA treated with ionizing radiation (10) and of guanine residues modified at the N-7 position with bulky alkylating agents (12). The molecular cloning of the fpg+ gene of E. coli (8), the purification of the Fpg protein (9), and the isolation of a bacterial mutant defective in Fpg protein (4) were critical steps for studies of the biological significance of this protein.The Fpg protein exhibits a large substrate specificity, including imidazole ring-opened purines modified at the C-8 position by N-hydroxy-2-aminofluorene (3). The Fpg protein is a metalloprotein containing one zinc atom per monomer (9) and is endowed with a nicking activity which incises DNA at apurinic-apyrimidinic (AP) sites (38). The biological importance of this enzyme is suggested by the fact that Fapy-DNA glycosylase activities have been conserved in prokaryotes (7) and eukaryotes (29,33) and that the imidazole ringopened form of N7-methylguanine residues in DNA is a potentially lethal lesion (6, 37). However, the lack of sensitivity of the E. coli mutant defective in Fpg protein to methylating agents suggested that imidazole ring-opened N7-methylguanine is not a biological substrate and/or that these residues are excised ...

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“…At wavelengths shorter than 290 nm the DNA directly absorbs the energy and the majority of photoproducts produced involve the pyrimidine bases. On the other hand, at wavelengths in the UV-A region (320-400 nm) the primary photochemical target is guanine (2)(3)(4)(5). The latter reactions occur through the agency of endogenous and exogenous photosensitizers, which are initially excited to the triplet state and generate oxidation products via their decay to the ground state through two principal competitive mechanisms labelled Type I and Type I1 (6).…”

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confidence: 99%