Effects of puromycin on DNA chain elongation in mammalian cells

Gautschi, J.R.

doi:10.1016/0022-2836(74)90224-1

Cited by 33 publications

(15 citation statements)

References 12 publications

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“…Some claim that, as with cycloheximide, the rate of chain elongation is significantly reduced without any change in the pattern of initiation (Gautschi, 1974). Others say that the elongation rate is affected, but not enough to account for the drop in overall DNA synthesis (Hand & Tamm, 1972.…”

Section: B Inhibitors Of Dna Synthesismentioning

confidence: 99%

“…In many instances, when protein synthesis is reduced by 950/0 or more, DNA synthesis is quickly reduced to less than 20% of the normal amount (Brega et al, 1968;Ensminger & Tamm, 1970;Gautschi, 1974), but in other cases it is reduced only to between 500/0 and 20% of the control (Ennis & Lubin, 1964;Young, 1966;Grollman, 1969;Chung & Coffee, 1969;Hyodo et al , 197 I;Seale & Simpson, 1975). Weintraub and Holtzer (1972) Gale et a!., 1972).…”

Section: Inhibitor Smentioning

confidence: 99%

“…1970;Ensminger & Tamm, 1970;Chung & Coffee, 1971;Hand & Tamm, 1972Hori and Lark, 1973;Gautschi, 1974).…”

Section: Inhibitor Smentioning

confidence: 99%

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Discontinuous DNA Synthesis in Mammalian Cells

Huberman¹,

Horwitz²

1974

Cold Spring Harbor Symposia on Quantitative Biology

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Section: B Inhibitors Of Dna Synthesismentioning

confidence: 99%

Section: Inhibitor Smentioning

confidence: 99%

See 1 more Smart Citation

Discontinuous DNA Synthesis in Mammalian Cells

Huberman¹,

Horwitz²

1974

Cold Spring Harbor Symposia on Quantitative Biology

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“…This hypothesis is supported by the observation that the drug exerts a stronger inhibitory effect on the maturation of replicons than on the total protein synthesis. Finally, this interpretation might explain some of the results which have been reported on the effect of the various protein synthesis inhibitors on the DNA synthesis and which till now have been considered controversial [3,15,27,28].…”

Section: Resultsmentioning

confidence: 98%

Effect of Cycloheximide on Maturation of Replicative Intermediates into High‐Molecular‐Weight DNA in Tetrahymena

Westergaard¹,

Marcker²,

Leer³

1978

European Journal of Biochemistry

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Replicative intermediates of discrete size ( z 41 S) are observed in the eukaryotic organism Tetrahymena pyriformis, when the organism is grown under defined physiological conditions. The intermediates (believed to represent replicons) are synthesized and accumulated over longer periods of time ( < 90 min), if the cells are treated with low concentrations of cycloheximide. Under these conditions the rate of total DNA synthesis is only slightly inhibited (< 15 %), while maturation of intermediate DNA into high-molecular-weight DNA is completely blocked ( > 98 7:). Cycloheximide appears to inhibit the maturation process more specifically than other protein synthesis inhibitors.Studies of the accumulated intermediates on alkaline buoyant density gradients demonstrate that initiation of new putative replicons occurs during treatment with cycloheximide. At present little is known about the processes that control the overall replication in eukaryotes. Unlike prokaryotes in which DNA synthesis is dependent upon protein synthesis only for the initiation of replicons [8,9], inhibition of protein synthesis in higher eukaryotes seems to affect both initiation ofan S period and completion of a replicative cycle [3,10-161. The inability of cells to complete the replicative cycle in the presence of protein synthesis inhibitors might arise from the complexity of genome since duplication must require coordinated synthesis and assembly of DNA, histones and non-histone proteins into the functional deoxyribonucleoprotein matrix. An alternative explanation for the reduced rate in replication might be the effect of protein synthesis inhibitors on the metabolism of deoxyribonucleotides [17].In this paper we report studies on the synthesis and maturation of defined replicative intermediates ( z 41 S, believed to represent replicons) in the eukaryotic organism Tetrahymena pyriformis. In agreement with previous reports on HeLa cells [16], we observe an accumulation of these intermediates in the presence of cycloheximide. In contrast to observations in higher cells, we do not observe a marked reduction in the rate of the total DNA synthesis. The results are discussed in relation to the overall control of DNA replication. EXPERIMENTAL PROCEDURE Culture of CellsTetrahymenapyriformis, amicronucleate strain GL, was grown at 28 "C in a defined medium [18,19] with low concentrations of phosphates (0.04 mM) and with omission of uridine from the medium. Instead, protease peptone and yeast extract were added to final concentrations of 0.04 % and 0.004 %, respectively.In standard experiments the cells were grown in the medium for 18 -20 h with an average generation time of about 7 h. In standard experiments the cultures were prelabelled with [14C]thymidine (0.02 pC/ml),

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“…These agents are also known to cause megaloblastic anemia in vivo. Becauise the rate of replication fork movement is also reduced by the protein synthesis inhibitors cycloheximide (41) and puromycin (42), the possibility that the lesions in DNA synthesis associated with megaloblastic anemila result from a less specific disturbance of cellular metabolism cannot be ruled out. However, it is well known that RNA and protein synthesis are relatively intact in megaloblasts compared with DNA synthesis (11).…”

Section: Resultsmentioning

confidence: 99%