Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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A single nuclear gene mutation has been isolated from strain 123.1C of Saccharomyces cerevisiae which is conditionally deficient in mitochondrial DNA metabolism. Growth of the haploid in media containing dextrose, a repressing carbon source, at 36 degrees C causes the rapid cessation of mitochondrial DNA synthesis as analyzed by radioactive 3H-adenine incorporation into mitochondrial DNA. These cells continue to grow and divide giving rise to neutral petites which are devoid of mitochondrial DNA as measured by radioactive incorporation of 3H-adenine at the permissive temperature. Growth of the haploid cells in media containing glycerol, a non-repressing carbon source, at 36 degrees C does not prevent mitochondrial DNA synthesis, however, the population of cells becomes partially petite. When such petites are analyzed, they are found to be suppressive and to contain mitochondrial DNA as measured in the manner described above. The action of this mutated gene appears to involve the sunthetic aspects of mitochondrial DNA metabolism, as haploid cells prelabeled in dextrose media with 3H-adenine show no loss or degradation of mitochondrial DNA at the restrictive temperature of 36 degrees C.
Mol Gen Genet 1977 Nov 04
PMID:Regulation of yeast mitochondrial DNA synthesis. I. Analysis of a mutant conditionally deficient in mitochondrial DNA metabolism. 34 Aug 91

The mutant uvsrho 72 of Saccharomyces cerevisiae UV-sensitive for rho- production displays slower growth on media containing non-fermentable carbon sources such as glycerol or lactate. The slower growth on glycerol is not due to any deficiency in glycerol catabolism or mitochondrial oxidative phosphorylation. No modifications of the sensitivity to ethidium bromide of the mitochondrial ATPase activity could be detected. A mathematical model is presented which accounts for slower growth of uvsrho 72 on the sole basis of the continuous and elevated rho- production in the mutant strain. This model, which estimates the rate of mutation from the rate of growth and vice versa, has been verified experimentally in the case of of usvrho 72. The model has been generalised, so that it can be used for any microbial population subject to constant and high rates of any type of mutation providing that the mutant is stable, and either unable to grow or able to grow at this own rate different from that of the parental strain.
Mol Gen Genet 1978 Aug 17
PMID:Basis for slow growth on the non-fermentable substrates by a Saccharomyces cerevisiae mutant UV-sensitive for rho- production. 36 46

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.
Mol Gen Genet 1979 Jun 20
PMID:Mitochondrial activity of 2,6-diaminopurine in Saccharomyces cerevisiae. 38 52

Nineteen haploid yeast (Saccharomyces cerevisiae) strains were used to assess the relative growth inhibitory potencies on fermentable vs. non-fermentable media of a collection of carcinogenic and non-carcinogenic chemicals. The majority of carcinogens were distinctly more potent on the non-fermentable (glycerol) medium, where mitochrondrial function is required for growth, than on the fermentable medium, where it is not. The anti-mitochondrial selectivity indicated by these growth tests was much slighter for the non-carcinogens. Similarly most carcinogens induced the cytoplasmic petite mutation whereas the non-carcinogens did not. Five carcinogens which were tested impaired the development of cytochromes aa3 and b in glucose cultures. Six carcinogens, when tested, inhibited growth on three fermentable sugars, the utilisation of which requires mitochondrial function. Out of five carcinogens which were examined, four suppressed the surface-dependent phenomenon of fluocculence in a flocculating strain of yeast, at concentrations primarily affecting the mitochondrial system; the fifth had a similar but less pronounced effect.
Mol Gen Genet 1979 Jul 02
PMID:Toxic and mutagenic effects of carcinogens on the mitochondria of Saccharomyces cerevisiae. 38 60

We have isolated about five hundred temperature-sensitive mutants specific for the mitochondrial functions. Their growth on glycerol is defective at 36 degrees C and/or 20 degrees C. While most of the mutations were nuclearly inherited, about thirty were found to be of mitochondrial origin. 1) Four mitochondrial mutations (three cryosensitive, one thermosensitive) were localized close to chloramphenicol and erythromycin resistance loci of the mitochondrial DNA, that is in the region coding for the 23 S ribosomal RNA. One of the mutation interfered with the expression of the chloramphenicol resistance gene. 2) A dozen nuclear mutations were isolated from a strain which is labelled with mitochondrial drug resistance markers (chloramphenicol, erythromycin, and paromomycin). Among the temperature sensitive respiratory deficient mutants, we have selected the mutations that supress the resistant phenotypes. We describe two non allelic such mutations, one being cryosensitive, the other thermosensitive. Both supress the expression of the mitochondrial chloramphenicol resistance gene. The temperature sensitive growth on glycerol and the modified antibiotic phenotype segregated together as a single recessive mutation. A biochemical study of these mutants is presented in a joint paper, confirming their presumed ribosomal nature.
Mol Gen Genet 1979
PMID:Mitochondrial and nuclear mutations that affect the biogenesis of the mitochondrial ribosomes of yeast. I. Genetics. 39 14

A method to detect low levels of interstrand cross-links in DNA of Saccharomyces cerevisiae is described. Isopycnic ultracentrifugation of alkali-treated, unpurified Eaton press homogenates allows the detection of less than one cross-link per yeast chromosome. Efficient separation of single- and double-stranded DNA requires low cell density and addition of glycerol during homogenization. Using a yeast strain defective in excision repair, a dose dependent formation of interstrand cross-links after treatment of cells with biological doses of nitrogen mustard, Triaziquone and Chloramubil could be demonstrated. The most powerful of these alkylating agents is Triziquone: half of the DNA molecules are shown to be cross-linked after a 12 min exposure to 9 X 10(-9) g/ml of the drug. The cross-linking reaction continues after excessive alkylating agent is removed. After having reached a maximum the fraction of renaturable DNA decreases upon further incubation. The speed of this "after-reaction" depends on temperature: 48 h after the end of treatment renaturability of DNA has almost completely disappeared when cells are kept at 36 degrees C.
Mol Gen Genet 1979 Oct 02
PMID:Formation and fate of cross-links induced by polyfunctional anticancer drugs in yeast. 39 49

The kinetics of dexamethasone binding to L 809 E cell line cytosol have been investigated by means of the protamine sulfate precipitation assay. The KDeq for dexamethasone was 1.1--3.3 nM. Binding was specific for glucocorticoids. The mean association rate constant (k+1) was 8.5 x 10(5) M-1 x min-1 and the dissociation rate constant was 4.6 x 10(-5) min-1 at 0 degrees C. The concentration of binding sites was 0.3 pmol/mg of cytosol protein. Binding kinetics were compatible with a model of positive cooperativity. The receptor sedimented at 7.5--9 S in glycerol gradients. By a combination of calibrated ultracentrifugation and polyacrylamide gel electrophoresis, a Stokes radius of 8.5 nm, a molecular weight of 268 000 daltons and a frictional ratio of 1.8 were determined in low ionic strength conditions. When the cells were incubated with 10 nM [3H]dexamethasone for 1 h, a more than 90% depletion of cytosol receptor and an equivalent accumulation of nuclear dexamethasone--receptor complexes was observed.
Mol Cell Endocrinol 1979 Mar
PMID:Glucocorticoid receptor in human embryo fibroblasts. I. Kinetic and physicochemical properties. 44 83

When peripheral lymphocytes stimulated with phytohemagglutinin were permeabilized in vitro, (3H) dCTP acted as a precursor for DNA synthesis, but the formation of a compound soluble in organic solvents could also be demonstrated. The structure of the latter compound was studied analyzing the products formed after alkaline hydrolysis or an enzymatic treatment with nucleotide pyrophosphatase. Both treatments led to the formation of (3H)dCMP. When stimulated lymphocytes were labeled in vivo with (14C)glycerol before permeabilization and ulterior labeling with (3H)dCTP a double labeled compound was obtained. When this compound was submitted to alkaline hydrolysis, (3H)dCMP and (14C)glycerol-3-phosphate were obtained. It was concluded that the compound soluble in organic solvents was phosphatidyl-dCMP.
Mol Cell Biochem 1979 Apr 02
PMID:Synthesis of phosphatidly-dCMP in permeabilized normal human lymphocytes. 46 Jan 75

The mobility of separate sites of the water-protein matrix depending on temperature and degree of hydration has been investigated by means of spin labels covalently attached to surface layers of proteins (alpha-chymotrypsin and human serum albumin) and also by a spin probe in a hydrophobic "pocket" of human serum albumin. The results obtained are compared with the data on the mobility of gamma-resonance labels (57Fe) firmly bound with the protein matrix in the same samples. At certain temperature and degree of hydration both spin and gamma-resonance label show an increase in mobility. With the degree of hydration increasing one may observe a simultaneous increase in energy and in entropy of activation: rotatory diffusion of spin labels, i. e., a compensation effect takes place which confirms the concept expressed earlier that cooperation of water-protein interactions is the main reason of CEF. It should be noted that at P/PS greater than 0.8 the values of delta E =7 divided by 10 kcal/mole, and delta S not equal to = 9 divided by 11 e. e. are specific to glycerol-like systems, i. e., under these conditions (P/Ps greater than 0.8) the water-protein layer has glycerol-like properties.
Mol Biol (Mosk)
PMID:[Effect of temperature and degree of hydration on the mobility of spin labels in surface layers of proteins]. 46 Feb 2

The formation of glycerol occurs when a solution of DL-glyceraldehyde is heated in the presence of hydrogen sulfide at room temperature. DL-glyceraldehyde and dihydroxyacetone treated with hydrazine, as well as DL-glyceraldehyde incubated with formaldehyde are also partially converted to glycerol. The yields of the above reactions are from approximately 1% to about 3%. The formation of glycerophosphates occurs when glycerol is heated with ammonium dihydrogen phosphate and either urea or cyanamide. The yield of glycerophosphates is about 30%, most of which is sn-glycero-1 (3)-phosphate. These findings indicate that glycerol and sn-glycero-3-phosphate, which are moieties of glycerolipids, could have been formed under conditions which may have prevailed on the primitive Earth.
J Mol Evol 1979 Dec
PMID:Cyanamide mediated synthesis under plausible primitive earth conditions. VI. The synthesis of glycerol and glycerophosphates. 53 3


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