The tautomeric state of N(4)-hydroxy- and of N(4)-amino-cytosine derivatives

Brown, D. M.; Hewlins, M. J. E.; Schell, Peter

doi:10.1039/j39680001925

Cited by 70 publications

(55 citation statements)

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“…In the case of a methoxycytosine analogue, similar incorporation occurred during in vitro polymerization (Singer et al, 1984;Reeves & Beattie, 1985). N 4 -methoxycytidine also prefers an imino form in solution (Brown et al, 1968;Morozov et al, 1982). A DNA fragment containing this residue was examined by X-ray analysis (Meervelt et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity

Chatake

Sunami

Ono

et al. 1999

Acta Crystallogr D Biol Cryst

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The DNA dodecamer of (CGCGmo 6 AATCCGCG) containing 2 Hdeoxy-N 6 -methoxyadenosine has been crystallized for X-ray analysis in order to investigate the effects of the modi®ed adenosine on base pairing. It has been found that the crystal changes from one form to another during data collection in a manner similar to a phase transition. The two crystal structures show that this phenomenon, ascribed to differences in humidity, is correlated with a change in the contact angle between the two duplexes.

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Section: Introductionmentioning

confidence: 99%

Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity

Chatake

Sunami

Ono

et al. 1999

Acta Crystallogr D Biol Cryst

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“…One likely mechanism is through point mutation. The list of reactions capable of causing such change is long, including cleavage of the glycosyl bond leading to apurinic and apyrimidinic sites (AP sites) (35), changes in tautomeric equilibrium (36,37) and ionization, and addition of alkyl groups to base nitrogens and oxygens (7). Both replicating and transcribing enzymes have been used in vitro to ascertain such changes.…”

Section: Effect Of Alkyl Derivatives On Transcription and Replicationmentioning

confidence: 99%

In Vivo Formation and Persistence of Modified Nucleosides Resulting from Alkylating Agents

Singer¹

1985

Environmental Health Perspectives

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Alkylating agents are ubiquitous in the human environment and are continuously synthesized in vivo. Although many classes exist, interest has been focused on the N-nitroso compounds, since many are mutagens for bacteria, phage, and cells, and carcinogens for mammals. In contrast to aromatic amines and polyaromatic hydrocarbons which can react at carbons, simple alkylating agents react with nitrogens and oxygens: 13 sites are possible, including the internucleotide phosphodiester. However, only the Nnitroso compounds react extensively with oxygens. In vivo, most possible derivatives have been found after administration of methyl and ethyl nitroso compounds. The ethylating agents are more reactive toward oxygens than are the methylating agents and are more carcinogenic in terms of total alkylation. This is true regardless of whether or not the compounds require metabolic activation. It has been hypothesized that the level and persistence of specific derivatives in a "target" cell correlates with oncogenesis. However, no single derivative can be solely responsible for this complex process, since correlations cannot be made for even a single carcinogen acting on various species or cell types. Some derivatives are chemically unstable, and the glycosyl bond is broken (3-and 7-alkylpurines), leaving apurinic sites which may be mutagenic. These, as well as most adducts, are recognized by different enzymatic activities which remove/ repair at various rates and efficiencies depending on the number of alkyl derivatives, as well as enzyme content in the cell and recognition of the enzyme. Evaluation of human exposure requires early and sensitive methods to detect the initial damage anid the extent of repair of each of the many promutagenic adducts.

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“…In the imino form, it can base pair with adenine ( Fig. 1 (5). This high proportion of a tautomer is in contrast to the situation with 5-bromodeoxyuridine, which is often referred to as having a significant tautomeric shift, but its tautomenc equilibrium constant between the keto and enol forms is l0-3 3 (14).…”

Section: Resultsmentioning

confidence: 54%

Induction of mutation in mouse FM3A cells by N4-aminocytidine-mediated replicational errors.

Takahashi¹,

Nishizawa²,

Negishi³

et al. 1988

Mol. Cell. Biol.

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To explore the potential use of a nucleoside analog, N4-aminocytidine, in studies of cellular biology, the mechanism of mutation induced by this compound in mouse FM3A cells in culture was studied. On treatment of cells in suspension with N4-aminocytidine, the mutation to ouabain resistance was induced. The major DNA-replicating enzyme in mammalian cells, DNA polymerase a, was used to investigate whether the possible cellular metabolite of N4-aminocytidine, N4-aminodeoxycytidine 5'-triphosphate (dCa`TP), can be incorporated into the DNA during replication. Using [3H]dCIUTP in an in vitro DNA-synthesizing system, we were able to show that this nucleotide analog can be incorporated into newly formed DNA and that it can serve as a substitute for either dCTP or dTTP. dCarTP in the absence of dCTP maintained the activated calf thymus DNA-directed polymerization of deoxynucleoside triphosphates as efficiently as in its presence. Even in the presence of dCTP, dCarTP was incorporated into the polynucleotide. When dCaITP was used as a single substrate in the poly(dA)-oligo(dT)-directed polymerase reaction, it was incorporated into the polynucleotide fraction. The extent of incorporation was 4% of that of dTTP incorporation when dTTP was used as a single substrate. Even in the presence of dTTP, dCaNTP incorporation was observed. A copolymer containing N4-aminocytosine residues was shown to incorporate guanine residues opposite the N4-aminocytosines. However, we were unable to observe adenine incorporation opposite N4-aminocytosine in templates. These cell-free experiments show that an AT-to-GC transition can take place in the presence of dCarTP during DNA synthesis, strongly suggesting that the mutation induced in the FM3A cells by N4-aminocytidine is due to replicational errors.

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The tautomeric state of N(4)-hydroxy- and of N(4)-amino-cytosine derivatives

Cited by 70 publications

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Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity

Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity

In Vivo Formation and Persistence of Modified Nucleosides Resulting from Alkylating Agents

Induction of mutation in mouse FM3A cells by N4-aminocytidine-mediated replicational errors.

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The tautomeric state of N(4)-hydroxy- and of N(4)-amino-cytosine derivatives

Cited by 70 publications

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Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo6AATCCGCG) containing 2′-deoxy-N 6-methoxyadenosine: change in crystal packing with different humidity

Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo6AATCCGCG) containing 2′-deoxy-N 6-methoxyadenosine: change in crystal packing with different humidity

In Vivo Formation and Persistence of Modified Nucleosides Resulting from Alkylating Agents

Induction of mutation in mouse FM3A cells by N4-aminocytidine-mediated replicational errors.

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Product

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Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity

Crystallization and preliminary analysis of a DNA dodecamer of d(CGCGmo⁶AATCCGCG) containing 2′-deoxy-N ⁶-methoxyadenosine: change in crystal packing with different humidity