Interferon inhibition of DNA synthesis and cell division

1972 ◽  
Vol 18 (2) ◽  
pp. 145-151 ◽  
Author(s):  
M. V. O'Shaughnessy ◽  
S. H. S. Lee ◽  
K. R. Rozee
Keyword(s):  
Cell Division ◽  
Antiviral Activity ◽  
Dna Synthesis ◽  
S Phase ◽  
Cell Suspensions ◽  
Depression Effect ◽  
Growth Depression ◽  
Synchronized Cells ◽  
Inhibition Of Dna Synthesis ◽  
New Protein

Using monodispersed cell suspensions, interferon preparations were shown to have both a lethal and a growth-depression effect in the same concentration range as that required for antiviral activity. In addition, synchronized cells treated with interferon respond by delaying their normal uptake of thymidine during S phase until after a period during which new protein is synthesized. Puromycin added during this period prevents both the synthesis of this protein and the subsequent synthesis of DNA.

Inhibition of DNA synthesis and cell division by a cell surface sialoglycopeptide

1989 ◽  
Vol 139 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Heideh Fattaey ◽  
Terry C. Johnson ◽  
Hsin-Hwei Chou
Keyword(s):  
Cell Division ◽  
Cell Surface ◽  
Dna Synthesis ◽  
A Cell ◽  
Inhibition Of Dna Synthesis

scholarly journals Nonperiodic Activity of the Human Anaphase-Promoting Complex–Cdh1 Ubiquitin Ligase Results in Continuous DNA Synthesis Uncoupled from Mitosis

2000 ◽  
Vol 20 (20) ◽  
pp. 7613-7623 ◽  
Author(s):  
Claus Storgaard Sørensen ◽  
Claudia Lukas ◽  
Edgar R. Kramer ◽  
Jan-Michael Peters ◽  
Jiri Bartek ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Ubiquitin Ligase ◽  
Mammalian Cells ◽  
Kinase Inhibitor ◽  
Cyclin B1 ◽  
S Phase ◽  
Anaphase Promoting Complex

ABSTRACT Ubiquitin-proteasome-mediated destruction of rate-limiting proteins is required for timely progression through the main cell cycle transitions. The anaphase-promoting complex (APC), periodically activated by the Cdh1 subunit, represents one of the major cellular ubiquitin ligases which, in Saccharomyces cerevisiae andDrosophila spp., triggers exit from mitosis and during G1 prevents unscheduled DNA replication. In this study we investigated the importance of periodic oscillation of the APC-Cdh1 activity for the cell cycle progression in human cells. We show that conditional interference with the APC-Cdh1 dissociation at the G1/S transition resulted in an inability to accumulate a surprisingly broad range of critical mitotic regulators including cyclin B1, cyclin A, Plk1, Pds1, mitosin (CENP-F), Aim1, and Cdc20. Unexpectedly, although constitutively assembled APC-Cdh1 also delayed G1/S transition and lowered the rate of DNA synthesis during S phase, some of the activities essential for DNA replication became markedly amplified, mainly due to a progressive increase of E2F-dependent cyclin E transcription and a rapid turnover of the p27Kip1 cyclin-dependent kinase inhibitor. Consequently, failure to inactivate APC-Cdh1 beyond the G1/S transition not only inhibited productive cell division but also supported slow but uninterrupted DNA replication, precluding S-phase exit and causing massive overreplication of the genome. Our data suggest that timely oscillation of the APC-Cdh1 ubiquitin ligase activity represents an essential step in coordinating DNA replication with cell division and that failure of mechanisms regulating association of APC with the Cdh1 activating subunit can undermine genomic stability in mammalian cells.

scholarly journals Effect of inhibition of DNA synthesis on u.v. sensitive Bs strains ofEscherichia coli

1969 ◽  
Vol 14 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Michael H. L. Green ◽  
John Donch ◽  
Young S. Chung ◽  
Joseph Greenberg
Keyword(s):  
Escherichia Coli ◽  
Cell Division ◽  
Dna Synthesis ◽  
Nalidixic Acid ◽  
Specific Inhibitor ◽  
Ofescherichia Coli ◽  
Inhibition Of Dna Synthesis ◽  
Division Mechanism

The effect of nalidixic acid, a specific inhibitor of DNA synthesis, onEscherichia colistrain B (lon) and its u.v.-sensitive derivatives is examined. Strain B itself is sensitive to nalidixic acid, whereas its u.v.-resistant derivative B/r is resistant.It is shown that in allexr Astrains, in which u.v.-induced filamentation is suppressed, resistance to nalidixic acid is increased. Amongexr Astrains, Bs4 is exceptionally resistant to nalidixic acid. This is because nalidixic acid kills only growing cells and strain Bs4, atryauxotroph, may grow poorly under the conditions used to test nalidixic acid.Theuvrgenes of the HCR strains Bs1, Bs8 and Bs12 do not suppress u.v.-induced filamentation nor do they affect the response to nalidixic acid. Theuvrgene of strain Bs3 is unusual in increasing the tendency to filament and also sensitivity to nalidixic acid.Strains Bs1, Bs3 and Bs8 are all doubly mutated from strain B, the second mutation (notuvr) being responsible for their increased resistance to nalidixic acid as well as partially or completely suppressing filamentation.It is concluded that the cell division mechanism of (lon) strain B is sensitive to inhibition of DNA synthesis. Mutations which suppress the tendency of strain B to filament reduce its sensitivity to inhibition of DNA synthesis.

Inhibition of DNA synthesis and cell division in Salmonella typhimurium by azide

1974 ◽  
Vol 135 (4) ◽  
pp. 339-348 ◽  
Author(s):  
Z. Cieśla ◽  
Krystyna Mardarowicz ◽  
T. Klopotowski
Keyword(s):  
Cell Division ◽  
Dna Synthesis ◽  
Salmonella Typhimurium ◽  
Inhibition Of Dna Synthesis

Induction of Cyclin E and Inhibition of DNA Synthesis by the Novel Acronycine Derivative S23906-1 Precede the Irreversible Arrest of Tumor Cells in S Phase Leading to Apoptosis

2001 ◽  
Vol 60 (6) ◽  
pp. 1383-1391 ◽  
Author(s):  
Stéphane Léonce ◽  
Valérie Pérez ◽  
Stéphanie Lambel ◽  
Delphine Peyroulan ◽  
François Tillequin ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Tumor Cells ◽  
Cyclin E ◽  
S Phase ◽  
The Novel ◽  
Inhibition Of Dna Synthesis

Hydroxyurea: Inhibition of DNA-Synthesis and Selective Susceptibility of S-Phase Cells In Vivo

1967 ◽  
Vol 17 (1) ◽  
pp. 5-8 ◽  
Author(s):  
F. S. Philips ◽  
H. S. Schwartz ◽  
S. S. Sternberg
Keyword(s):  
Dna Synthesis ◽  
Renal Excretion ◽  
Tissue Concentration ◽  
Tritiated Thymidine ◽  
S Phase ◽  
Cell Renewal ◽  
Cytotoxic Effects ◽  
Inhibition Of Dna Synthesis ◽  
Physiological Disposition

SummaryThe cytotoxic effects of hydroxyurea and of related hydroxamic acid derivatives in vivo are briefly described. They occur selectively in tissues with high rates of cell renewal and they are of brief duration. Tissue concentration of hydroxyurea diminish rapidly as the result of renal excretion and metabolism; there is a close temporal relation between the physiological disposition of the agents and the cytotoxic changes. Hydroxyurea induces an immediate inhibition of DNA synthesis in proliferating tisdsues such as thymus, small intestine, and regenerating liver. Autoradiographic studies of mouse duodenum using tritiated thymidine have shown that the lethal susceptibility to hydroxyurea is restricted to cells in the S-phase of the mitotic cycles. Cells in G1, G2, and M are not damaged by the agent.

scholarly journals Transient inhibition of DNA synthesis results in increased dihydrofolate reductase synthesis and subsequent increased DNA content per cell.

1986 ◽  
Vol 6 (10) ◽  
pp. 3373-3381 ◽  
Author(s):  
R N Johnston ◽  
J Feder ◽  
A B Hill ◽  
S W Sherwood ◽  
R T Schimke
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Gene Amplification ◽  
Dihydrofolate Reductase ◽  
Dna Content ◽  
S Phase ◽  
Phase Cell ◽  
Drug Inhibition ◽  
Specific Proteins ◽  
Inhibition Of Dna Synthesis

We examined the role that blockage of cells in the cell cycle may play in the stimulation of gene amplification and enhancement of drug resistance. We found that several different inhibitors of DNA synthesis, which were each able to block cells at the G1-S-phase boundary, induced an enhanced cycloheximide-sensitive synthesis of an early S-phase cell cycle-regulated enzyme, dihydrofolate reductase, and of other proteins as well. This response was specific, in that blockage at the G2 phase did not result in overproduction of the enzyme. When the cells were released from drug inhibition, DNA synthesis resumed, resulting in a cycloheximide-sensitive elevation in DNA content per cell. We speculate that the excess DNA synthesis (which could contribute to events detectable later as gene amplification) is a consequence of the accumulation of S-phase-specific proteins in the affected cells, which may then secondarily influence the pattern of DNA replication.

A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division

1994 ◽  
Vol 107 (1) ◽  
pp. 253-265 ◽  
Author(s):  
I.T. Todorov ◽  
R. Pepperkok ◽  
R.N. Philipova ◽  
S.E. Kearsey ◽  
W. Ansorge ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Amino Acid ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Mammalian Cells ◽  
Nuclear Protein ◽  
Amino Acid Level ◽  
S Phase ◽  
Significant Similarity

Molecular cloning and characterisation of a human nuclear protein designated BM28 is reported. On the amino acid level this 892 amino acid protein, migrating on SDS-gels as a 125 kDa polypeptide, shares areas of significant similarity with a recently defined family of early S phase proteins. The members of this family, the Saccharomyces cerevisiae Mcm2p, Mcm3p, Cdc46p/Mcm5p, the Schizosaccharomyces pombe Cdc21p and the mouse protein P1 are considered to be involved in the onset of DNA replication. The highest similarity was found with Mcm2p (42% identity over the whole length and higher than 75% over a conservative region of 215 amino acid residues), suggesting that BM28 could represent the human homologue of the S. cerevisiae MCM2. Using antibodies raised against the recombinant BM28 the corresponding antigen was found to be localised in the nuclei of various mammalian cells. Microinjection of anti-BM28 antibody into synchronised mouse NIH3T3 or human HeLa cells presents evidence for the involvement of the protein in cell cycle progression. When injected in G1 phase the anti-BM28 antibody inhibits the onset of subsequent DNA synthesis as tested by the incorporation of bromodeoxyuridine. Microinjection during the S phase had no effect on DNA synthesis, but inhibits cell division. The data suggest that the nuclear protein BM28 is required for two events of the cell cycle, for the onset of DNA replication and for cell division.

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