Histidine regulatory mutants in Salmonella typhimurium

Roth, John R.; Antón, Dora N.; Hartman, Philip

doi:10.1016/0022-2836(66)90134-3

Cited by 225 publications

(47 citation statements)

References 14 publications

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“…The 1242 mutation allows production of 12-fold the normal amounts of histidine enzymes (11). Revertants of this 305S strain were induced by spotting a drop of mutagen solution on enriched minimal agar spread plates by the method of Ames (2).…”

Section: Methodsmentioning

confidence: 99%

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Isono

Yourno

1974

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

138

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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 -G-G-G--C-C-C-. The polycyclic carcinogens tested (e.g., 2-nitroso- Frameshift mutations result from additions (+) or deletions (-) of DNA base pairs from genes encoding polypeptide chains, so that triplets in the product mRNA are not read in the correct frame after the mutation (7,8). Correction of such mutations may occur by restoration of the original base sequence, or by introduction of a closely positioned frameshift of opposite sign. In these double frameshift mutants (+ -) the normal reading frame is restored in mRNA except for the segment between the two frameshifts. The (+ -) mRNA segment encodes a segment of altered amino acids in the polypeptide chain, often disturbing its function. Sequencing the affected polypeptide segment allows reconstruction of associated mRNA and DNA sequences (9, 10). The hisD gene encodes the enzyme histidinol dehydrogenase (EC 1.1.1.23). To determine nucleic acid base changes in 3052 caused by polycyclic carcinogens and other frameshift mutagens, we have induced reversion in 3052 by these compounds. Revertants carrying double frameshift mutations were detected by rapid screening of crude extracts from revertants for altered histidinol dehydrogenase. The altered enzyme from each double mutant was then purified and compared with the normal enzyme by peptide mapping to detect altered peptides. These were sequenced to reconstruct altered DNA sequences in 3052 and its revertants. We have also classified the reversions with respect to certain properties of histidinol dehydrogenase from crude extracts, and have correlated the classes of reversion with specific DNA sequence changes.We believe that this newly characterized tester system will be useful for rapid screening of carcinogens as frameshift mutagens. For the relatively small effort of inducing reversions in 3052 with carcinogens or other mutagens and examining crude extract histidinol dehydrogenase, it should be possible to assign the reversions to the standard groups with known base sequence changes in DNA (see below).

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Section: Methodsmentioning

confidence: 99%

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Isono

Yourno

1974

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

138

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“…Histidinol dehydrogenase was isolated from Salmonella typhimurium strain LT-2 his0 1242 [9]. The organism was grown in the minimal medium of Vogel and Bonner [lo] supplemented with 0.4 "/, glucose and 0.2 nutrient broth.…”

Section: Enzyme Preparationmentioning

confidence: 99%

Evidence for an Essential Lysine at the Active Site of l‐Histidinol : NAD⁺ Oxidoreductase; a Bifunctional Dehydrogenase

Bürger¹,

Görisch²

1981

European Journal of Biochemistry

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Histidinol dehydrogenase (EC 3 .I .I .23) from Salrnonellu typhimurium is inhibited by formaldehyde and pyridoxal 5-phosphate (pyridoxal-P). E-Pyridoxyl-lysine is isolated upon acid hydrolysis of pyridoxal-P-treated enzyme reduced by sodium borohydride. In the presence of formylhistidinol and formylhistidine (specific ligands of the enzyme) inactivation of histidinol dehydrogenase by pyridoxal-P is prevented. Extrapolation of the initial part of the inactivation curve caused by pyridoxal-P indicates that modification of two essential lysine residues results in inactivation of the dimeric enzyme. The essential lysine residues appear to participate in the reversible oxidation/reduction reaction converting histidinol to histidinal.Histidinol dehydrogenase catalyzes the four-electron oxidation of the amino alcohol L-histidinol to the corresponding amino acid L-histidine [I].

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“…Histidinol dehydrogenase was isolated from S. typhimurium strain LT-2 hisO 1242 (Roth et al, 1966) obtained through the courtesy of Dr. Roth, Johns Hopkins University, Baltimore, MD, U.S.A. The organism was grown in the minimal medium of Vogel & Bonner (1956) supplemented with 0.4% glucose and 0.2% nutrient broth.…”

Section: Enzyme Preparationmentioning

confidence: 99%

The catalytically active form of histidinol dehydrogenase from Salmonella typhimurium

Bürger¹,

Görisch²,

Lingens³

1979

Biochemical Journal

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Histidine regulatory mutants in Salmonella typhimurium

Cited by 225 publications

References 14 publications

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Evidence for an Essential Lysine at the Active Site of l‐Histidinol : NAD⁺ Oxidoreductase; a Bifunctional Dehydrogenase

The catalytically active form of histidinol dehydrogenase from Salmonella typhimurium

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Histidine regulatory mutants in Salmonella typhimurium

Cited by 225 publications

References 14 publications

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Chemical Carcinogens as Frameshift Mutagens: Salmonella DNA Sequence Sensitive to Mutagenesis by Polycyclic Carcinogens

Evidence for an Essential Lysine at the Active Site of l‐Histidinol : NAD+ Oxidoreductase; a Bifunctional Dehydrogenase

The catalytically active form of histidinol dehydrogenase from Salmonella typhimurium

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Evidence for an Essential Lysine at the Active Site of l‐Histidinol : NAD⁺ Oxidoreductase; a Bifunctional Dehydrogenase