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J Yourno

Publications and source records attributed to J Yourno.

35 records · Page 2Linked to original sources
PubMed1974

Chemical carcinogens as frameshift mutagens: Salmonella DNA sequence sensitive to mutagenesis by polycyclic carcinogens.

Other investigators have shown that several polycyclic carcinogens are frameshift mutagens in Salmonella. Mutagenic potency of these compounds is assessed by ability to induce reversion of histidine-requiring frameshift mutants to prototrophy. One frameshift mutation in the histidinol dehydrogenase gene, hisD3052, is unusually sensitive to mutagenesis by certain polycyclic carcinogens. We find that the 3052 mutation is a - 1 deletion, probably loss of a G.C pair from a DNA repeat of [unk]. The polycyclic carcinogens tested (e.g., 2-nitroso-fluorene) revert 3052 by deleting a [unk] doublet from the DNA sequence [unk], which is close to the 3052 site. This rare mispairing-prone sequence represents the carcinogen-sensitive "hotspot" in 3052. The ICR compounds, noncarcinogenic intercalating agents, show a broader specificity of mutagenesis. Reversion with these mutagens occurs predominantly by two mechanisms: one identical to that of the polycyclic carcinogens, and the other by +1 additions in a third DNA tract narrowly separated from the 3052 site. The alkylating carcinogen N-methyl-N'-nitro-N-nitrosoguanidine appears to have a similar dual specificity. DNA base changes in 3052 revertants have been correlated with properties of histidinol dehydrogenase in crude extracts. This correlation of DNA base sequence with electrophoretic and other properties of the mutant proteins allows one to analyze easily the specificity of new mutagens that mutate this strain.

Acridines↗
PubMed1972

Externally suppressible proline quadruplet ccc U.

Three (+1) frameshift mutations located at different genetic sites respond with high specificity to the same external suppressor. In each case, the suppressor restores small amounts of protein that is normal in electrophoretic mobility and heat stability. One of these proteins has been shown to have the wildtype amino acid sequence. The messenger RNA quadruplet CCCUappears to be common to all three frameshift sites and to be translated by the suppressor as proline. A likely suppressor agent is a proline transfer RNA with a quadruplet anticodon or its functional equivalent.

Alcohol Oxidoreductases↗
PubMed1970

Reversion of the frameshift hisD3018 of Salmonella typhimurium.

Previous studies on histidinol dehydrogenase from His(+) revertants have shown that the frameshift mutation hisD3018 is a +1 type, resulting from inclusion of an extra cytidylate residue in messenger ribonucleic acid. Histidinol dehydrogenase from newly isolated spontaneous and N-methyl-N'-nitro-N-nitrosoguanidine (NG)-induced intragenic revertants has been examined for amino acid replacements. The results provide additional evidence that NG can delete guanine plus cytosine base pairs from deoxyribonucleic acid. One spontaneous revertant was found to result from a +2 addition of approximately 16 nucleotide residues before the +1 parent frameshift, and another by a -4 deletion about six residues before the same. Circumstantial evidence suggests the in vivo codon assignment GAG for glutamic acid. A region of histidinol dehydrogenase highly permissive of amino acid changes encoded in the minus (-) phase is now apparent.

Acrylates↗
PubMed1969

Externally suppressible frameshift mutant of Salmonella typhimurium.

Prototrophic revertants of ICR-191A-induced frameshift mutant hisD3018 have been induced spontaneously by ICR-191A and N-methyl-N'-nitro-N-nitrosoguanidine (NG) treatment. In each case two genetically distinct prototroph classes were differentiated by transducibility into his deletion recipients: (i) transducible, generally fast-growing revertants within the hisD gene producing from 10 to 100% of normal amounts of histidinol dehydrogenase and (ii) nontransducible slow-growing prototrophs with very low levels of enzyme activity of which at least some arose by external suppression. These nontransducible revertants, whether arising spontaneously or in the presence of ICR-191A or NG, contain histidinol dehydrogenase which is electrophoretically similar to the wild-type enzyme.

Acridines↗
PubMed1969

Nature of the hisD3018 frameshift mutation in Salmonella typhimurium.

Histidinol dehydrogenase from three differing revertants of ICR-191A-induced frameshift hisD3018 has been purified and examined for amino acid replacements. The enzyme from one spontaneously arising revertant, R7, contains an extra proline residue, whereas that from another, R5, contains an extensive frameshifted sequence, four amino acid residues of which have been identified to date. The amino acid replacement data are in agreement with the in vitro code word assignments and allow the characterization of the hisD3018 frameshift as an addition of one nucleotide pair, most likely guanine plus cytosine. Enzymatic data for those ICR-191A-induced revertants of hisD3018 arising within the hisD gene indicate that the enzyme is wild type and, therefore, that ICR-191A can cause deletions as well as additions of single base pairs. The wild-type amino acid sequence is restored in enzyme from an N-methyl-N'-nitro-N-nitrosoguanidine (NG)-induced revertant, R29, suggesting that NG is a base-deleting as well as a base-substituting mutagen. The unusual response of hisD3018 to external suppressors is considered in terms of reinitiation of protein synthesis out of phase, coupled with suppression of a nonpermissive missense codon so generated, and of an alternative hypothesis invoking a true frameshift suppressor transfer ribonucleic acid with an extended or deleted anticodon.

Acridines↗