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At least 19 recordsLinked to original sources
PubMed1977

2-Aminopurine-induced mutagenesis in T4 bacteriophage: a model relating mutation frequency to 2-aminopurine incorporation in DNA.

We measured the in vivo incorporation of 2-aminopurine into DNA of T4 bacteriophage allelic for gene 43 (DNA polymerase), mutator (L56), 43+, and antimutator (L141). The magnitude of incorporation (mol/mol of Thy) was 1/1500 in L56, 1/1600 in 43+, and 1/8900 in L141. The incorporation ratio L56:43+:L141 in vivo was equal to that mediated by the purified DNA polymerases of these allelic phages in vitro. A model for 2-aminopurine-induced A-T in equilibrium G-C transitions is discussed. The model is used to predict the magnitudes of replication errors (C mispairing with a template 2-aminopurine) and incorporation errors (2-aminopurine mispairing with a template C) per round of replication and to investigate the asymmetry in 2-aminopurine-induced transitions favoring the A-T leads to G-C pathway over G-C leads to A-T. We suggest that the fidelity of L56 and L141 DNA polymerases exemplifies one-step and two-step editing, respectively.

2-Aminopurine↗
PubMed1977

Attempts to induce mutations in Haemophilus influenzae with the base analogues 5-bromodeoxyuridine and 2-aminopurine.

Attempts were made to induce mutations in Haemophilus influenzae with the base analogues 5-bromodeoxyuridine and 2-aminopurine. These attempts were unsuccessful. Incorporation studies with BrdUrd showed, in agreement with earlier studies on Escherichia coli, that BrdUrd was discriminated against when dThd was also present but was incorporated to essentially the same extent as dThd when only BrdUrd was present. In this latter case, strands fully substituted with BrdUrd was produced, but survival data suggest that bacteria deriving their DNA by replication on such fully substituted templates were inviable. However, bacteria with about 20% of the thymine substituted with bromouracil were usually viable. No mutations could be detected in the descendants of such bacteria. The reasons for this are discussed and it is concluded that in all probability the replication system in species rarely if every treats incorporated bromouracil as anything except a thymine analogue. The alternative possibility, that the negative results are a consequence of the absence of the reclex (SOS) error-prone repair system in this species, is considered much less likely.

2-Aminopurine↗
PubMed1976

The synthesis and properties of N6-substituted 2-amino-purine derivatives.

1. The synthesis, ultraviolet absorption spectra, and behaviour in alkali of N6-methoxy-, N6-methyl, hydroxy-, and N6-hydroxy-2-aminopurines have been described 2. N6-Methoxy-2-aminopurine riboside 5'-pyrophosphate has been prepared and used for polymerization with polynucleotide phosphorylase. 3. The copolymer containing N6-methoxy-2-aminopurine riboside and adenosine residues has been obtained; attempts to synthesize the homopolymer have not been successful. 4. All the purine analogues synthesized have been tested and shown to act mutagenically on Salmonella typhimurium TA1530.

Hydrogen-Ion Concentration↗
PubMed1978

The efficiency and extent of mutagenic activity of some new mutagens of base-analogue type.

N4-Hydroxycytidine, 5-methyl-N4-hydroxydeoxycytidine and 2-amino-N6-hydroxyadenine were tested for their mutagenic activity in S. typhimurium and E. coli cells. Reversion analysis of different markers was applied in a plate-test system, and 2-aminopurine was used as a reference mutagen. (i) 2-Amino-N6-hydroxyadenine was the most potent mutagen. In some cases it gave more than 1000 colonies of revertants per plate. (ii) N6-Hydroxycytidine was the least specific mutagen. Almost all the tested markers were inducible to revert by this analogue. (iii) The mutagenic specificity of 5-methyl-N4-hydroxydeoxycytidine seemed to be opposite to that of 2-aminopurine. This suggests that the former can induce transition of CG to TA. (iv) A comparison of the mutagenic actions of N4-hydroxycytidine and 5-methyl-N4-hydroxy-deoxycytidine showed that deoxyriboside analogues are not necessarily more efficient mutagens than ribonucleosides. (v) No purine or pyrimidine deficiency was needed for mutagenesis to occur for any of the mutagens investigated. (vi) The results on bacteria with different repair abilities suggest that base-analogue mutagenesis (except perhaps for BrdUrd) occurs mainly during replication of nucleic acids containing substituted nucleosides with bi-functional specificity.

2-Aminopurine↗
PubMed1978

R plasmid-mediated enhancement of mutagenesis in strains of Escherichia coli deficient is known repair functions.

The response to four mutagens (UV radiation, methyl methanesulfonate (MMS), cis-platinum dichlorodiamine (cis-PDD), and a 2-aminopurine (AP)) known to cause different types of DNA damage was investigated in the WP2 strain wild-type for DNA repair and in uvrA-, lexA-, polA-, uvrD- and recL- strains. Each strain was also tested after introduction of either the pKM101 or R648 plasmid. The number of revertants produced by a given mutagen in a given bacterial strain depended in a complex way on: (1) the nature of the mutagen and the type of lesion it created in DNA; (2) the prensence and the nature of defects in the chromosomally determined DNA-repair system; and (3) the presence and the nature of plasmids with mutator effect. The results confirm that plasmids enhance mutagenesis through an error-prone DNA-repair system, which is expressed at different levels for different plasmids. Or, alternatively, different repair mechanisms for different plasmids may exist.

2-Aminopurine↗
PubMed1976

Altered nutritional requirements associated with mutations affecting the structures of ribonucleic acid polymerase in Lactobacillus casei.

Rifampin-resistant mutants were isolated from Lactobacillus casei S1 and examined for possible simultaneous alteration in nutritional properties. Among the 36 mutants obtained either spontaneously or after mutagenesis with 2-aminopurine, 22 were found to be altered with respect to the specific growth requirements. The majority (20 of 22) of the latter mutants were shown to require L-glutamine in addition to the nutrients required by the parental strain for maximal growth, whereas the remaining mutants had apparently lost the requirement for L-aspartate. Further studies with one of the glutamine-requiring mutants revealed that the rifampin resistance of this strain is due to the resistance of ribonucleic acid polymerase itself and that a single mutation is responsible for both rifampin resistance and the glutamine requirement. These results strongly indicate that a structural alteration of the ribonucleic acid polymerase caused by the rifampin resistance mutation somehow affected glutamine metabolism, possibly through change in selective transcription of the genes involved.

2-Aminopurine↗
PubMed1977

Isolation, genetic analysis, and characterization of Escherichia coli mutants with defects in the lacY gene.

Five hundred thirty-five lacY mutants were isolated from an Escherichia coli strain carrying the lactose operon on an F' factor, either without mutagenesis or after mutagenesis with 2-aminopurine or N-methyl-N'-nitro-N-nitrosoguanidine. Crosses against 48 independently isolated deletions ending in the lacY gene divided the gene into 36 deletion groups. Suppressibility studies with 7 nonsense suppressor strains classified 276 mutants as nonsense mutants and 78 as missense (or nonsuppressible) mutants. One hundred seventy-nine mutants were "leaky" and could not be so allocated, and two were found to have small internal deletions. Nonsense mutants could in many cases be subdivided even within deletion groups on the basis of their suppressibility pattern, giving a total of 70 groups of nonsense mutants. Studies of these mutants allow the following conclusions: lactose and melibiose most probably do not have separate binding sites on the permease; the lacY region most likely consists of one cistron, and so both active transport and facilitated diffusion are functions of one protein; and finally, there is probably no small defined region of the permease responsible for energy coupling of transport. Furthermore, the strains and the analysis form the basis for a future functional study of the permease by biochemical techniques.

2-Aminopurine↗
PubMed1978

Mutagenicity testing of benomyl, methyl-2-benzimidazole carbamate, streptozotocin and N-methyl-N'-nitro-N-nitrosoguanidine in Salmonella typhimurium in vitro and in rodent host-mediated assays.

The fungicide benomyl and its commercial preparations Fundazol 50WP and Benlate 50WP and the benomyl metabolite methyl-2-benzimidazole carbamate and its commercial preparation MBC 50WP were tested for mutagenicity in in vitro spot tests, in microsomal plate assay, in liquid-culture treatments, or in rodent host-mediated assay. The base-pair substitution Salmonella typhimurium mutant hisG46 and the hisG46-bearing uvrB excision-repair-deficient mutants TA100, TA1530, TA1535 or TA1950 were used as test organisms. Complete genotypic information of these mutants is given in Ames et al. [2]. Captain 50WP, streptozotocin (SZN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-aminopurine and N-acetylaminofluorene were used as positive control compounds. In nonoverlay spot tests Benlate 50WP was not mutagenic over a dose range of 50-5000 microgram/spot in hisG46 and TA1535. In overlay spot tests 50 or 100 microgram/spot Benomyl, MBC, Fundazol 50WP, Benlate 50WP and MBC 50WP were tested in hisG46, TA1530 or TA1950. Only a non-commercial MBC sample at 100 microgram/spot showed weak mutagenic activity in hisG46. In microsomal activation plate assay MBC, benomyl, Fundazol 50WP and Benlate 50WP were tested in TA100 over a dose range of 50-2000 microgram/plate. None of the compounds showed mutagenicity. In a 20-h liquid-culture treatment 10, 100, 1000 and 10 000 microgram/ml Fundazol 50WP were not mutagenic in TA 30. In 1-h liquid-culture treatments benomyl, Benlate 50WP or Fundazol 50WP failed to induce mutations in hisG46, TA100 or TA1950 over a dose range of 0.25-1000 microgram/ml. Appropriate positive controls were mutagenic in each experiment. The consistently negative results in this study with commercial MBC and benomyl preparations are contrary to positive results reported earlier with similar methods and similar commercial preparations. Possible reasons to explain the different results are presented. The alkylating agents SZN and MNNG induced fewer mutations in TA1530 and TA1950 uvrB excision-repair-deficient strains than in the hisG46 excision-proficient strain, indicating that with these mutagens excision-repair is also a mutation-prone process. In rodent host-mediated assays with Fundazol 50WP in mice 3 consecutive subcutaneous hourly doses of 500 mg/kg in hisG46 and TA1950 and in rats or mice an oral dose of 4000 mg/kg in TA1950 were not mutagenic. The positive control SZN was mutagenic.

Animals↗
PubMed1977

The stereochemical basis of template function.

The behavior of nucelotides with thioketo-substituted pyrimidine bases (4-thiouracil, 2-thiouracil and 2-thiocytosine) or amino-analogue purine bases (2-aminopurine and 2,6-diaminopurine) in transcription and translation was investigated. The experimental results obtained led to the following conclusions. 1. The stereochemical basis of substrate selection in transcription is the geometry of Watson-Crick base pairs A-U (or A-T) and G-C between substrate and template bases. 2. The topology of the active site of Escherichia coli RNA polymerase is precisely adopted to the geometry of Watson-Crick base pairs. 3. The enzyme active site discriminates between A-U (A-T) and G-C base pairs. An essential feature in this discrimination is the 6-NH2 group of the A-U (A-T) base pair and the 2-keto group of cytosine in the G-C base pair. 4. The codon properties of a nucleic acid base in messenger RNA can be predicted on the basis of its specificity in polynucleotide interactions. There seems to be no evidence for the participation of protein topological sites in the control of the specificity of codon-anticodon interactions in translation.

Animals↗
PubMed1979

Mitochondrial activity of 2,6-diaminopurine in Saccharomyces cerevisiae.

2,6-diaminpurine (DAP) selectively inhibited mitochondrial protein synthesis in yeast cells with concomitant failure of cells to grow in non-fermentable (yeast extract, glycerol) medium. The selectivity was pronounced in all strains tested (15) nearly all of which were able to grow in yeast extract, glucose medium containing 5 mg/ml DAP (maximum solubility) whereas growth was arrested in all strains at 250-500 microgram/ml DAP in the glycerol medium. The inhibition was reversed by further addition of adenine to the culture medium. RNA synthesis in rat liver mitochondria was depressed by DAP suggesting that the analogue affected RNA polymerase activity. There was no evidence of nuclear mutagenicity by DAP but resistance to the antibiotics chloramphenicol and oligomycin was induced by the drug. Genetic evidence, although limited, indicated that the resistance mutations were cytoplasmic. The mitochondrial petite mutation was also induced by DAP but only at comparatively high concentrations. The mutagenic effects were seen only in the glycerol medium.

2-Aminopurine↗
PubMed1978

Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance.

E. coli strains carrying the dam-3 and dam-4 mutations resulting in reduced levels of 6-methyladenine in the DNA have been found to be more sensitive to base analogue mutagenesis than dam+ strains. Mutagenesis by EMS was also found to be enhanced in dam- strains. Dam- mutants however were not found to be hypermutable by UV light. It is concluded that the dam- strains are deficient in the correct repair of mispairing lesions. The data are consistent with the hypothesis that 6-methyladenine residues in the DNA are involved in strand discrimination during mismatch correction.

2-Aminopurine↗
PubMed1978

Molecular basis of base substitution hotspots in Escherichia coli.

In the lacI gene of Escherichia coli spontaneous base substituion hotspots occur at 5-methylcytosine residues. The hotspots disappear when the respective cytosines are not methylated. We suggest that the hotspots may result from the spontaneous deamination of 5-methylcytosine to thymine, which is not excised by the enzyme DNA-uracil glycosidase.

2-Aminopurine↗
PubMed1977

Search for revertants of the glutamine mischarging mutans of Escherichia coli su+3 tyrosine suppressor tRNA that are able to insert tyrosine at the site of amber mutation.

We have isolated a bacterial amber mutation (nadam) that is suppressed by the tyrosine inserting suppressor su+3 but not by the glutamine (su+2, su+3 A1, su+3 G82 and su+3 A1G82), serine (su+1) and leucine (su+6) inserting suppressors. The su+7 suppressor which inserts glutamine and tryptophan also suppresses this mutation indicating that tryptophan, in addition to tyrosine, is accepted at the site of amber mutation. We have used this amber mutation to search for revertants of the su+3 glutamine mischarging mutants su+3 A1, su+3 G82 and su+3 A1G82 that are able to insert tyrosine at the site of amber mutation. Two types of revertants were found in the case of su+3 A1. One type corresponding to the true revertant A1 leads to G, and the other to the second site revertants C81 leads to U (A1U81). The A1U81 revertant has been shown to insert both glutamine and tyrosine at the site of amber mutation. Only true revertants (G82 leads to A) were obtained when su+3 G82 was analyzed. No revertants were obtained in the case of the su+3 A1G82. These results are discussed in relation to aminoacyl-tRNA recognition.

2-Aminopurine↗
PubMed1977

Ochre suppression in Salmonella typhimurium.

A bacterial strain was constructed which permitted positive selection for ochre suppressor mutations as well as for the loss of suppressor function. A derivative bearing an ochre suppressor mutation was selected following mutagenesis with N-methyl-N-nitroso-N'-nitroguanidine. The suppressor-bearing strain was treated with nitrous acid to eliminate suppressor function by mutation, and a strain lacking suppressor activity was selected. The selected strain which had lost suppressor function was then subjected to mutagenesis to induce a second suppressor mutation. The alternating sequence (induction of an ochre suppressor mutation leads to induction of a mutation eliminating ochre suppressor activity) was repeated 29 and one-half times in a single strain. Some of the suppressor mutations were tentatively mapped at four locations on the chromosome. The first suppressor mutation selected maps at about minute 30 on the chromosome. The second suppressor selected maps at approximately minute 60, while the third suppressor maps nearby, possibly as far as minute 72. Among the subsequently selected suppressor mutations, all eleven which were mapped were cotransducible with the gal and nic loci near minute 36 on the chromosome and may represent more than one suppressor gene. Deletions were selected which inactivate two of the ochre suppressor alleles mapping near the gal-nic region, suggesting that one or more such genes are dispensable. Some evidence also suggests that the occurrence of either deletion mutations or transduction-mediated recombination events in the gal-nic region can cause instability of nearby suppressor alleles.

2-Aminopurine↗
PubMed1977

[Genetic control of Escherichia coli K-12 strains' assimilation of 2,6-diaminopurine as a purine source].

Mutations of the resistance to 2,6-diaminopurine (apt), which affect adenine phosphoribosyltransferase, fail to permit the growth of Escherichia coli pur mutants (purine auxotrophs which cannot make inosine monophosphate de novo) on the medium with 2,6-diaminopurine (DAP) as the sole source of purines. Addition of a small amount of hypoxantine, but not guanine, stimulated the growth of mutants of pur apt and pur apt+ genotypes on the medium with DAP. The utilization of DAP as purine source in the presence of hypoxantine is blocked by mutations guaC (guanosine monophosphate reductase), add (adenosine deaminase) and pup (purine necleoside phosphorylase), suggesting that DAP are utilized via purine nucleoside phosphorylase and adenosine deaminase. The drm mutation (that increases the level of pentose-1-phosphate in the cell) does not activate the utilization of DAP. The results indicate that a step, that limits the utilization of DAP as the sole source of purines by pur mutants of E. coli, is the deamination of DAP nucleoside.

2-Aminopurine↗