New reaction of adenine and cytosine derivatives, potentially useful for nucleic acids modification.

Kochetkov, N. K.; Shibaev, V. N.; Kost, A. A.

doi:10.1016/s0040-4039(01)96762-0

Cited by 185 publications

(82 citation statements)

References 3 publications

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“…First described in 1971, etheno adducts in DNA (Fig. 3) are generated by the reaction of bases in DNA with lipid peroxidation products or xenobiotics such as vinyl chloride or urethane (75,76). Although differentials in the mutagenic potency of etheno adducts have been demonstrated in different model systems, there is extensive evidence to support the hypothesis that etheno adducts are mutagenic (reviewed in Ref.…”

Section: Adducts As Biomarkers Of Carcinogenesis and Chemopreventionmentioning

confidence: 99%

Biological Relevance of Adduct Detection to the Chemoprevention of Cancer

Sharma

Farmer

2004

Clinical Cancer Research

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Section: Adducts As Biomarkers Of Carcinogenesis and Chemopreventionmentioning

confidence: 99%

Biological Relevance of Adduct Detection to the Chemoprevention of Cancer

Sharma

Farmer

2004

Clinical Cancer Research

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“…1). These were first identified as reaction products of nucleobases with chloroacetaldehyde (18) and were used as fluorescent analogs in biochemical studies and as probes for nucleic acid structures (19 -21). The ⑀ DNA adducts were subsequently recognized as reaction products of DNA with reactive metabolites of several genotoxic chemicals, including the carcinogens vinyl chloride and vinyl carbamate (an oxidation product of urethane).…”

mentioning

confidence: 99%

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Zhao

Pence

Christov

et al. 2012

Journal of Biological Chemistry

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N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG.

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“…Both bromoacetaldehyde and its less potent analog chloroacetaldehyde react specifically at the N-1 and N-6 positions of adenine and the N-3 and N4 positions of cytosine residues (13)(14)(15)(16), when these bases are not hydrogen bonded (17,18). Although less reactive, the N-1 and N-2 positions of guanine residues also react with chloroacetaldehyde (19).…”

mentioning

confidence: 99%

Magnesium ion-dependent triple-helix structure formed by homopurine-homopyrimidine sequences in supercoiled plasmid DNA.

Kohwi

Kohwi‐Shigematsu²

1988

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

310

192

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DNA can be chemically cleaved at the site of chloroacetaldehyde-modified residues by the chemicals used for Maxam-Gilbert sequencing reactions. Use of this technique facilitates fine structural analysis of unpaired DNA bases in DNA with non-B-DNA structure. This method was used to study the non-B-DNA structure adopted by the poly-(dG)-poly(dC) sequence under torsional stress at various ionic conditions. In the presence of 2 mM Mg2+, the 5' half of the deoxycytosine tract is very reactive to chloroacetaldehyde, while the 3' half is virtually unreactive. In the poly(dG) tract, chloroacetaldehyde reaction is restricted to the center guanine residues. In the absence of Mg2+, however, it is the 5' halfofthe deoxyguanine tract that is reactive to chloroacetaldehyde, while the 3' half is unreactive. And chloroacetaldehyde reaction is restricted to the center cytosine residues in the poly(dC) stretch. These results strongly suggest that the poly(dG)-poly(dC) sequence is folded into halves from the center of the sequence to form a tetra-stranded-like structure. Such a structure contains either a triplex consisting of poly(dG) poly(dG) poly(dC) strands in the presence of Mg2+ or a triplex consisting of poly(dC)-poly(dG)'poly(dC) strands in the absence of Mg2+. The fourth strand, not involved in triplex formation, is closely associated with the triplex and is positioned in such a way that DNA bases are exposed and freely accessible to the chloroacetaldehyde reaction.The torsional stress that results from negative supercoiling is relieved through the formation of non-B-form DNA structures. Under torsional stress, non-B-DNA structures are preferentially formed by certain DNA sequences. Homopurine/homopyrimidine sequences are one type of such DNA sequences known to adopt non-B-DNA structure in supercoiled DNA. Long stretches of homopurine/homopyrimidine are often found in putative regulatory regions of eukaryotic genes. The anomalous sensitivity of these homopurine/homopyrimidine sequences to S1 nuclease, when studied in supercoiled DNA, has been reported by a number of groups (1-9).We previously devised a method that used bromoacetaldehyde and chloroacetaldehyde to detect and analyze the altered DNA conformation of chromatin in vivo and in supercoiled DNA (10-12). Both bromoacetaldehyde and its less potent analog chloroacetaldehyde react specifically at the N-1 and N-6 positions of adenine and the N-3 and N4 positions of cytosine residues (13-16), when these bases are not hydrogen bonded (17, 18). Although less reactive, the N-1 and N-2 positions of guanine residues also react with chloroacetaldehyde (19). Using bromoacetaldehyde as the probe and then digesting the bromoacetaldehyde-modified sites with S1 nuclease after cleaving the DNA with a restriction enzyme, we have shown that the 16 contiguous guanine residues at -180 base pairs (bp) from the mRNA cap site of the chicken adult 3A-globin gene constitute one of the major sites detected by bromoacetaldehyde in supercoiled DNA but not in linear DNA (10). Furthermor...

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New reaction of adenine and cytosine derivatives, potentially useful for nucleic acids modification.

Cited by 185 publications

References 3 publications

Biological Relevance of Adduct Detection to the Chemoprevention of Cancer

Biological Relevance of Adduct Detection to the Chemoprevention of Cancer

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Magnesium ion-dependent triple-helix structure formed by homopurine-homopyrimidine sequences in supercoiled plasmid DNA.

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