Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from Escherichla coli

Chetsanga, Christopher J.; Lindahl, Thomas

doi:10.1093/nar/6.11.3673

Cited by 265 publications

(162 citation statements)

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“…In a recent study (5), the transformation of primary breast tumors to the metastatic state was shown to involve a Ͼ2-fold increase in ⅐OH damage in DNA, as indicated by modified nucleotide base models comprising mutagenic 8-hydroxyadenine (6) and the putatively nonmutagenic ring-opened product 4,6-diamino-5-formamidopyrimidine (fapyadenine; refs. [7][8][9][10][11]. In addition, plots of the modified nucleotide base model log 10 (fapyadenine͞8-hydroxyadenine) versus the size of metastatic and nonmetastatic breast tumors revealed that the metastatic tumor DNA had significantly greater structural diversity than the nonmetastatic tumor DNA (P ϭ 0.01; ref.…”

mentioning

confidence: 99%

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

Malins

Polissar

Gunselman

1996

Proc. Natl. Acad. Sci. U.S.A.

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Wavenumber-absorbance relationships of infrared spectra of DNA analyzed by principal components analysis may be expressed as points in space. Each point represents a highly discriminating measure of DNA structure. Structural modifications of DNA, such as those induced by free radicals, alter vibrational and rotational motion and consequently change the spatial location of the points. Using this technology to analyze breast tumor DNA, we revealed a 94؇ difference in direction between the progression of normal DNA 3 primary tumor DNA and the progression of primary tumor DNA 3 metastatic tumor DNA (P < 0.001). This sharp directional change was accompanied by a substantial increase in the structural diversity of the metastatic tumor DNA (P ‫؍‬ 0.003), which, on the basis of the volume of the core cluster of points, could comprise as many as 11 ؋ 10 9 different phenotypes. This suggests that the heterogeneity and varied physiological properties known to characterize malignant tumor cell populations may at least partially arise from these diverse phenotypes. The evidence suggests that the progression to the metastatic state involves structural modifications in DNA that are markedly different from the modifications associated with the formation of the primary tumor. Overall, the findings of this and earlier studies imply that the observed DNA alterations are a pivotal factor in the etiology of breast cancer and a formidable barrier to overcome in intervention to control the disease. In terms of cancer etiology and prediction, the technology described has potentially wide application to studies in which the structural status of DNA is an important consideration.A significant body of evidence points to the involvement of the hydroxyl radical (⅐OH) in introducing mutagenic structures into DNA of the normal female breast, thus statistically increasing the probability of breast cancer (1-5). In a recent study (5), the transformation of primary breast tumors to the metastatic state was shown to involve a Ͼ2-fold increase in ⅐OH damage in DNA, as indicated by modified nucleotide base models comprising mutagenic 8-hydroxyadenine (6) and the putatively nonmutagenic ring-opened product 4,6-diamino-5-formamidopyrimidine (fapyadenine; refs. 7-11). In addition, plots of the modified nucleotide base model log 10 (fapyadenine͞8-hydroxyadenine) versus the size of metastatic and nonmetastatic breast tumors revealed that the metastatic tumor DNA had significantly greater structural diversity than the nonmetastatic tumor DNA (P ϭ 0.01; ref. 5).Principal components analysis (PCA) of data obtained by Fourier transform-infrared (FT-IR) spectroscopy yielded plots in which individual spectra were represented as points in twoor three-dimensional space. Each point was a highly discriminating representation of an individual DNA structure in that spatially and visually close points had Ͻ3% average spectral difference over the range 1750-700 cm Ϫ1 (5). The core cluster of metastatic tumor DNA points was substantially larger than the core c...

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mentioning

confidence: 99%

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

Malins

Polissar

Gunselman

1996

Proc. Natl. Acad. Sci. U.S.A.

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“…Ames (1983) has drawn attention to the large number of environmental mutagens, including substances in food, which might act through the formation of oxygen radicals. Several repair enzymes that act on DNA exposed to oxidising agents have been characterised in our laboratory: these include (i) formamidopyrimidine-DNA glycosylase, which catalyses the release of potentially cytotoxic purine residues with an opened imidazole ring from y-ray-irradiated DNA (Chetsanga & Lindahl, 1979;Boiteux & Laval, 1983;Breimer, 1984); (ii) a separate DNA glycosylase which releases urea (a remnant of thymine) and several other derivatives with fragmented pyrimidine rings from oxidised DNA (Breimer & Lindahl, 1980 -this enzyme is identical with endonuclease III, which removes thymine glycol from DNA (Demple & Linn, 1980); (iii) a Mg2 + independent endonuclease for apurinic sites in DNA, endonuclease IV (Ljungquist et al, 1976;Ljungquist, 1977;Demple et al, 1986), which also removes 3-phosphoglycolate residues from 3' termini of damaged DNA. Two distinct DNA glycosylases with the specificities described are found both in E. coli and in human cells (Breimer, 1983(Breimer, , 1984.…”

Section: T Lindahlmentioning

confidence: 99%

The 1987 Walter Hubert lecture: Regulation and deficiencies in DNA repair

Lindahl

1987

Br J Cancer

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Summary A number of rare human inherited syndromes are associated with apparent defects in DNA repair and a greatly increased frequency of cancer. Cell lines derived from such individuals phenotypically resemble certain bacterial mutant strains that have increased sensitivity to radiation or chemical agents and well characterised repair defects. This analogy provides leads for unravelling the molecular alterations in such cancer-prone human cells. The inducibility of DNA repair enzymes is also reviewed. Exposure of bacteria to alkylating agents, or oxygen radicals, causes the overproduction of several novel and interesting repair activities, and the induced bacteria provide an abundant source of these proteins for purification and biological characterisation. Enzymes with the same defined specificities are often present in human cells, presumably serving the same functions as in microorganisms, but these activities are only constitutively expressed at low levels.

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“…It is known that the glycosylases can have multiple specificities. Bacterial FPG was first shown to act on ring-opened purines [4].…”

Section: Introductionmentioning

confidence: 99%

“…It is known that the glycosylases can have multiple specificities. Bacterial FPG was first shown to act on ring-opened purines [4].To test the specificities of the plant enzymes, we have inserted cDNAs for OGG and FPG from Arabidopsis thaliana into Escherichia coli strains, devised by Cupples and Miller [5] to test for single-base substitution mutations, in which the endogenous FPG gene has been inactivated [6]. There are six Cupples and Miller [5] strains, each with a base-pair substitution in its LacZ gene that inactivates the product b-galactosidase.…”

mentioning

confidence: 99%

Antimutagenic specificities of two plant glycosylases, oxoguanine glycosylase and formamidopyrimidine glycosylase, assayed in vivo

Murphy¹,

Guo²

2010

Biochemical and Biophysical Research Communications

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a b s t r a c tThe base-excision repair process protects genomes by removing and replacing altered bases in DNA. Two analogous glycosylases, oxoguanine glycosylase (OGG) and formamidopyrimidine glycosylase (FPG), can start the process by removing oxidized guanine, the most common modification that leads to misreading of DNA. Plants possess genes for both types of glycosylases. We have tested the hypothesis that the two enzymes in plants have diverged in their specificities by inserting the genes for each enzyme from Arabidopsis thaliana L. into Escherichia coli strains designed to indicate the frequencies of the six possible single-base changes. Both enzymes retain the ability to reduce the rate of GC ? TA transversion mutations. Both enzymes also reduce the frequency of two other base-change mutations, GC ? AT and AT ? TA. We do not find a divergence in the repair capabilities of the two enzymes, as measured in E. coli, although surprisingly FPG appears to increase the rate of mutations in one particular strain.Ó 2010 Elsevier Inc. All rights reserved. IntroductionModification of bases in DNA is a common occurrence in cells and one with potentially serious mutagenic consequences. One of the most common modifications is oxidation of guanine. 7,8-Dihydro-8-oxoguanine (8-oxo-G) base-pairs equally well with cytosine and adenine, leading to GC ? TA transversions. Virtually all organisms have a glycosylase that recognizes and removes 8-oxo-G from DNA, leading to its replacement by unmodified G through the subsequent reactions of the base-excision repair pathway. In archaea, fungi, and animals, the effective glycosylase is oxoguanine glycosylase (OGG); in bacteria, it is formamidopyrimidine glycosylase (FPG). Plants, uniquely, have genes for both enzymes. Furthermore, plant cells have variants of the mRNA for FPG produced by alternative splicing [1,2].The reason for the retention in plants of the genes for both OGG and FPG and the diversity of FPG variants is not known. It is reasonable to speculate that the presence of photosynthetic metabolism, with the resulting high concentration of diatomic oxygen and oxygen radicals, creates a particular need for protection of the genome against oxidative damage. However, knock-out mutants that lack genes for either OGG or FPG, or both, show no obvious phenotype over several generations [3], so the adaptive value of the genes must be subtle or important under unusual circumstances that have not yet been identified. It is also possible that the presence of two analogous genes has allowed one or both to alter the specificity of their protein products, allowing them to recognize additional base modifications. It is known that the glycosylases can have multiple specificities. Bacterial FPG was first shown to act on ring-opened purines [4].To test the specificities of the plant enzymes, we have inserted cDNAs for OGG and FPG from Arabidopsis thaliana into Escherichia coli strains, devised by Cupples and Miller [5] to test for single-base substitution mutations, in which the endogeno...

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Release of 7-methylguanine residues whose imidazole rings have been opened from damaged DNA by a DNA glycosylase from Escherichla coli

Cited by 265 publications

References 15 publications

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation

The 1987 Walter Hubert lecture: Regulation and deficiencies in DNA repair

Antimutagenic specificities of two plant glycosylases, oxoguanine glycosylase and formamidopyrimidine glycosylase, assayed in vivo

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