scholarly journals Lomofungin as an inhibitor of nucleic acid synthesis in Saccharomyces cerevisiae

1974 ◽  
Vol 142 (3) ◽  
pp. 457-463 ◽  
Author(s):  
Michael Cannon ◽  
Antonio Jimenez

1. The antibiotic lomofungin was found to be a potent inhibitor of both DNA and RNA synthesis in Saccharomyces cerevisiae. Under selected growth conditions inhibition of DNA synthesis by the drug preceded inhibition of RNA synthesis. 2. Although in general lomofungin inhibited synthesis of ribosomal RNA and polydisperse RNA more effectively than that of low-molecular-weight RNA, under certain conditions the drug inhibited almost completely synthesis of both 4S and 5S RNA. 3. Inhibition of both RNA and DNA synthesis may be explained if RNA synthesis is required for DNA synthesis in yeast. Alternatively, lomofungin, in addition to interacting with DNA-dependent RNA polymerase, might interfere with a component(s) of the DNA-synthetic apparatus. The drug may thus prove to be of considerable value in studies of DNA synthesis in eukaryotes.

1966 ◽  
Vol 44 (6) ◽  
pp. 839-852 ◽  
Author(s):  
D. K. Myers ◽  
Kirsten Skov

The rate of incorporation of thymidine into the deoxyribonucleic acid (DNA) of rat thymocytes in vitro was not immediately affected by low doses of X-radiation, but became progressively more inhibited as the irradiated cells were incubated at 37 °C for periods of up to 6 hours. Ribonucleic acid (RNA) synthesis deteriorated almost at the same rate as DNA synthesis after X-irradiation in vitro, but protein synthesis was slightly more resistant. Addition of 10–50 mM nicotinamide to the irradiated cell suspensions tended to retard the development of this inhibition, particularly at low temperatures, but high concentrations of nicotinamide were also toxic to these cells. The inhibition of DNA synthesis by X-irradiation appeared to follow a qualitatively similar pattern in thymus, spleen, and regenerating liver in vivo.In addition to the inhibition resulting from degenerative processes in the irradiated cells, DNA synthesis in vitro was directly inhibited by 20–30 kr X-radiation. The effects of radiation on DNA synthesis paralleled to some extent its effects on the gel-forming capacity of the deoxyribonucleoprotein from the thymus cells. It is suggested that the normal synthesis of both RNA and DNA in thymocytes depends on the integrity of the deoxyribonucleoprotein.


1971 ◽  
Vol 17 (4) ◽  
pp. 461-466 ◽  
Author(s):  
Hiroko Watanabe ◽  
Mamoru Watanabe

Infection of Escherichia coli by R23 results in a marked inhibition of rRNA synthesis. Both 16 S and 23 S RNA are inhibited with maximal inhibition occurring at 30 min. Inhibition of 4 S RNA is not as profound. DNA synthesis is also inhibited after R23 infection although infected cells continue to divide for about one generation (45–60 min) after infection.


1992 ◽  
Vol 284 (1) ◽  
pp. 47-52 ◽  
Author(s):  
P Landini ◽  
E Corti ◽  
B P Goldstein ◽  
M Denaro

Purpuromycin, an antibiotic active against both fungi and bacteria, shows different modes of action against these two kinds of micro-organisms; in Candida albicans it inhibits RNA synthesis, whereas in Bacillus subtilis protein synthesis is primarily affected, with DNA and RNA synthesis blocked at higher concentrations of the drug. In bacterial cell-free protein-synthesis systems, purpuromycin did not inhibit synthesis from endogenous mRNA (elongation of peptides initiated within the intact cell) but inhibited MS2-phase RNA-dependent protein synthesis (which requires initiation) by 50% at 0.1 mg/l. Poly(U)-directed polyphenylalanine synthesis was 50% inhibited by 20 mg of purpuromycin/l when added to a complete system; however, when purpuromycin was preincubated with ribosomes dissociated into 30 S and 50 S subunits, the concentration for 50% inhibition fell to 0.1 mg/l. By contrast, in a C. albicans cell-free system poly(U)-directed polyphenylalanine synthesis was partially inhibited only at 200 mg/l. Purpuromycin also inhibited polynucleotide synthesis in vitro in reactions using Escherichia coli or wheat-germ RNA polymerases or E. coli DNA polymerase I. We suggest that in bacteria the primary target of purpuromycin is on ribosomes and that its action precedes the elongation step of protein synthesis. The effect on nucleic acid synthesis in both fungi and bacteria may be due to interaction of purpuromycin with DNA.


1984 ◽  
Vol 49 (11) ◽  
pp. 2551-2556 ◽  
Author(s):  
Jiří Beránek ◽  
Edward M. Acton

Series of pyrimidine nucleoside analogs were tested for inhibition of DNA and/or RNA synthesis at L1210 cells. The structure-activity relationship was studied at the analogs of cancerostatic agents 5-fluorouracil and arabinosylcytosine. Out of them the 5'-chloro derivatives give some promise. The inhibitory activity of cyclocytidine vs DNA and RNA synthesis approaches the activity of cancerostatic antibotics.


Blood ◽  
1965 ◽  
Vol 25 (2) ◽  
pp. 197-203 ◽  
Author(s):  
LOIS B. EPSTEIN ◽  
GEORGE BRECHER

Abstract The percentages of mononuclear cells synthesizing DNA and RNA in serial studies of blood from 13 patients with infectious mononucleosis were determined. Early in the disease a high percentage of atypical lymphocytes were in DNA synthesis but this percentage decreased rapidly as the disease progressed. Late in the disease many atypical lymphocytes were still present but few, if any, were synthesizing DNA. Similar results were found for RNA synthesis. Presumably active proliferation of atypical cells in the tissues is restricted to an early period of the disease, whereas release of such atypical cells may continue for a considerable period.


Development ◽  
1973 ◽  
Vol 30 (1) ◽  
pp. 179-217
Author(s):  
Suzanne L. Ullmann

(i) Nurse cells and oocytes in the telotrophic ovary of Tenebrio molitor L. (Insecta, Coleoptera-Polyphaga) are differentiated in the larval stadium. (ii) During pupation DNA synthesis occurs in the nurse cells and is probably associated with polyploidy; some of them become multinucleate. The functional significance of these events is interpreted as preparation for subsequent massive RNA synthesis. (iii) The oviducts incorporate [3H]thymidine and undergo elongation due to mitoses. This ceases at eclosion. (iv) RNA synthesis in the pupal ovary is low, but increases in the nurse cells and follicle cells just prior to eclosion. (v) In the adult ovary, once the growth phase has been initiated, a primary oocyte takes about six days to reach maturity. (vi) The nurse cells, though apparently lacking nucleoli, synthesize much stable RNA which reaches each oocyte via a trophic cord. (vii) The follicle cells undergo continuous DNA synthesis: some nuclei contain over 64 times the haploid amount of DNA. Replication is probably asynchronous within a nucleus: this may account for the phenomenon of simultaneous DNA and RNA synthesis in the follicle cells, which also lack nucleoli. (viii) Oogenesis has been divided into nine developmental stages, three of which are vitellogenic. (ix) The oocyte chromosomes are capable of RNA synthesis both when despiralized during early previtellogenesis and after karyosome formation, which occurs at stage 6. (x) The protein content of the oocyte appears to have a dual origin: at least part of the ooplasmic proteins form in situ; while yolk proteins are derived from the haemolymph. The extra-ovarian protein reaches the oocyte via spaces which develop between the follicle cells. (xi) The nucleoplasm becomes more heavily labelled with proteins than the ooplasm. With [3H]leucine, methionine and phenylalanine but not with tryptophane or arginine, there is an increased incorporation into the karyosome. It is suggested that this karyosome-associated protein may function in gene masking. (xii) The significance of these findings is discussed with reference to the literature.


1977 ◽  
Vol 28 (1) ◽  
pp. 61-70
Author(s):  
L.B. Kass ◽  
D.J. Paolillo

Light stimulates the incorporation of [3H]uridine and [3H]thymidine in addition to plastid replication in germinating Polytrichum spores. Significant amounts of [3H]uridine and [3H]thymidine are incorporated in darkness but not to the same level as in light. Plastids continue to produce nucleic acids when their capacity to multiply is suspended due to the absence of light. However, a higher amount of DNA synthesis in the light is correlated with the result that chloroplast replication begins again in the light after prolonged dark incubation. An imperfect association of plastid replication and nucleic acid synthesis is suggested by the lack of stimulation of DNA synthesis by light during plastid replication in the first 8 h of incubation. A temporal separation can be demonstrated for chloroplast and nuclear DNA synthesis at the beginning of germination in Polytrichum spores, with DNA synthesis in the chloroplasts preceding that in the nucleus. The mitotic S phase is longer than 16 h for at least half of the nuclei.


1974 ◽  
Vol 61 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Nathan A. Berger ◽  
Sister Ann Marie Skinner

Lymphocyte cultures from all normal human adults are stimulated by zinc ions to increase DNA and RNA synthesis and undergo blast transformation. Optimal stimulation occurs at 0.1 mM Zn++. Examination of the effects of other divalent cations reveals that 0.01 mM Hg++ also stimulates lymphocyte DNA synthesis. Ca++ and Mg++ do not affect DNA synthesis in this culture system, while Mn++, Co++, Cd++, Cu++, and Ni++ at concentrations of 10-7–10-3 M are inhibitory. DNA and RNA synthesis and blast transformation begin to increase after cultures are incubated for 2–3 days with Zn++ and these processes reach a maximum rate after 6 days. The increase in Zn++-stimulated lymphocyte DNA synthesis is prevented by rendering cells incapable of DNA-dependent RNA synthesis with actinomycin D or by blocking protein synthesis with cycloheximide or puromycin. Zn++-stimulated DNA synthesis is also partially inhibited by 5'-AMP and chloramphenicol. Zn++ must be present for the entire 6-day culture period to produce maximum stimulation of DNA synthesis. In contrast to its ability to independently stimulate DNA synthesis, 0.1 mM Zn++ inhibits DNA synthesis in phytohemagglutinin-stimulated lymphocytes and L1210 lymphoblasts.


1971 ◽  
Vol 49 (2) ◽  
pp. 498-506 ◽  
Author(s):  
V. L. Rudick

Changes in the levels of DNA and RNA syntheses have been studied in unagitated cultures of Acanthamoeba castellanii during the phases of logarithmic multiplication (LM) and population growth deceleration (PGD). Pulse-labeling experiments show that the rate of DNA synthesis decreases at the same time that DNA per cell is known to drop by 50%. The drop in DNA content has been explained by demonstrating with hydroxyurea that the majority of LM amebas can replicate once when DNA synthesis is inhibited and, therefore, must be in G2, whereas the PGD amebas cannot multiply in the presence of inhibitor and, therefore, must be in G1. The inhibition of DNA synthesis in LM or PGD cells has been shown to induce encystment. The rate of RNA synthesis, as illustrated by pulse-labeling experiments, increases 25% in late LM-early PGD while RNA per cell increases 75%. The rate of synthesis then decreases 65%. The majority of accumulated RNA has been demonstrated to be ribosomal by disc electrophoresis. By using actinomycin D at different stages during the RNA build-up, the ability of the amebas to encyst has been shown to depend on the presence of this RNA. The observations on DNA and RNA are discussed with respect to the occurrence of cysts in the cultures during PGD.


Blood ◽  
1964 ◽  
Vol 24 (1) ◽  
pp. 69-75 ◽  
Author(s):  
LOIS B. EPSTEIN ◽  
FREDERICK STOHLMAN

Abstract RNA and DNA synthesis were measured in cultures of normal human peripheral blood using tritiated cytidine and thymidine and autoradiographic technics. RNA synthesis preceded DNA synthesis by 24 hours. RNA synthesis occurred predominantly in the large and medium-sized "blast-like" cells, but did occur, to a lesser extent, in the small lymphocytes. RNA synthesis did not occur in the absence of phytohemagglutinin, nor did DNA synthesis. Mechanisms of action of phytohemagglutinin are discussed with particular reference to its possible antigenic nature.


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