Physiological properties and repair of apurinic/apyrimidinic sites and imidazole ring-opened guanines in DNA

Laval, Jacques; Boiteux, Serge; O’Connor, Tim

doi:10.1016/0027-5107(90)90152-t

Cited by 41 publications

(20 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results suggest that these enzymes are identical and that the range of structures currently recognized as substrates for FPG protein (8) should be expanded. The base released during the reaction with 8-oxodG DNA was identified as 8-oxo-7,8-dihydroguanine .…”

mentioning

confidence: 77%

“…Purines undergo opening of the imidazole ring to create Fapy residues (18) or are hydroxylated at the C-8 position to form 8-oxodG and 8-oxodA (1,19). Imidazole ring-opening is facilitated by alkylation at N-7, followed by treatment with alkali, resulting in DNA containing Me-Fapy (5,8,20).…”

Section: Discussionmentioning

confidence: 99%

“…The general properties of this enzyme, designated 8-hydroxyguanine endonuclease, proved similar to those reported for the FPG protein of E. coli (4)(5)(6). The latter, also known as formamidopyrimidine (Fapy) DNA glycosylase, catalyzes release of imidazole ring-opened forms of guanine and adenine from alkylated or irradiated polynucleotides and DNA (4)(5)(6)(7)(8).…”

mentioning

confidence: 99%

See 2 more Smart Citations

8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

Tchou¹,

Kasai²,

Shibutani³

et al. 1991

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

682

433

View full text Add to dashboard Cite

Substrate specificities of FPG protein (also known as formamidopyrimidine DNA glycosylase) and 8-hydroxyguanine endonuclease were compared by using defined duplex oligodeoxynucleotides containing single residues of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxodA), and 2,6-diamino-4-hydroxy-5-(N-methyl)formamidopyrimidine (Me-Fapy). Duplexes containing 8-oxodG positioned opposite dC, dG, or dT were cleaved, whereas single-stranded DNA and duplexes containing 8-oxodGdA or 8-oxodA positioned opposite any of the four DNA bases were relatively resistant. Both enzymes cut duplexes containing 8-oxoG-dC 3' and 5' to the modified base but failed to cleave duplex DNA containing synthetic abasic sites, mismatches containing dG, or unmodified DNA. 8-Oxoguanine, identified by HPLC-electrochemical detection techniques, was released during the enzymatic reaction. Apparent Km values for FPG protein acting on duplex substrates containing a single Me-Fapy or 8-oxodG residue positioned opposite dC were 41 and 8 nM, respectively, and those for 8-hydroxyguanine endonuclease were 30 and 13 nM, respectively. Comparison of the properties of the two enzyme activities suggest that they are identical. In view of the widespread distribution of 8-oxodG in cellular DNA, the demonstrated miscoding and mutagenic properties of this lesion, and the existence of a bacterial gene coding for FPG protein, we propose that 8-oxodG DNA is the primary physiological substrate for a constituent glycosylase found in bacteria and mammalian cells.Active oxygen species, generated by ionizing radiation and by endogenous oxidation processes, react with deoxyguanosine (dG) residues in DNA to form 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) (reviewed in ref.

show abstract

mentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

Tchou¹,

Kasai²,

Shibutani³

et al. 1991

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

682

433

View full text Add to dashboard Cite

show abstract

“…For the Fpg and Nth proteins, spontaneous breaks (Ctrl) and enzymatic breaks observed in control oligomer (0 days of incubation at 37°C) were subtracted and thus represent only the amount of modified base, which was formed during incubation at 37°C. glycosylases participating in the repair of the oxidized bases, Fpg and Nth proteins (34,35). We surmise that the Fpg protein excises pyrimidine ring-opened isomer B2, because all known substrates of the enzyme are characterized by the presence of the carbonyl group, e.g.…”

Section: Discussionmentioning

confidence: 99%

The Pyrimidine Ring-opened Derivative of 1,N 6-Ethenoadenine Is Excised from DNA by theEscherichia coli Fpg and Nth Proteins

Speina

Cieśla

Wójcik

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

It was previously shown that 1,N 6 -ethenoadenine (⑀A) in DNA rearranges into a pyrimidine ring-opened derivative of 20-fold higher mutagenic potency in Escherichia coli (AB1157 lac⌬U169) than the parental ⑀A (Basu, A. K., Wood, M. L., Niedernhofer, L. J., Ramos, L. A., and Essigmann, J. M. (1993) Biochemistry 32, 12793-12801). We have found that at pH 7.0, the stability of the N-glycosidic bond in ⑀dA is 20-fold lower than in dA. In alkaline conditions, but also at neutrality, ⑀dA depurinates or converts into products: ⑀dA 3 B 3 C 3 D. Compound B is a product of water molecule addition to the C(2)-N(3) bond, which is in equilibrium with a product of N(1)-C(2) bond rupture in ⑀dA. Compound C is a deformylated derivative of ring-opened compound B, which further depurinates yielding compound D. Ethenoadenine degradation products are not recognized by human N-alkylpurine-DNA glycosylase, which repairs ⑀A. Product B is excised from oligodeoxynucleotides by E. coli formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease III (Nth). Repair by the Fpg protein is as efficient as that of 7,8-dihydro-8-oxoguanine when the excised base is paired with dT and dC but is less favorable when paired with dG and dA. Ethenoadenine rearrangement products are formed in oligodeoxynucleotides also at neutral pH at the rate of about 2-3% per week at 37°C, and therefore they may contribute to ⑀A mutations.

show abstract

“…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.

View full text Add to dashboard Cite

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...

show abstract

Physiological properties and repair of apurinic/apyrimidinic sites and imidazole ring-opened guanines in DNA

Cited by 41 publications

References 41 publications

8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

8-oxoguanine (8-hydroxyguanine) DNA glycosylase and its substrate specificity.

The Pyrimidine Ring-opened Derivative of 1,N 6-Ethenoadenine Is Excised from DNA by theEscherichia coli Fpg and Nth Proteins

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

Contact Info

Product

Resources

About