scholarly journals Nitrosative Stress Triggers Inhibition of DNA Synthesis and Translational Suppression of Positive Cell Cycle Regulators

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Robert J. Tomko ◽  
John S. Lazo
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Nitrosative Stress ◽  
Cell Cycle Regulators ◽  
Inhibition Of Dna Synthesis ◽  
Translational Suppression

Effect of inhibitors of DNA replication on early zebrafish embryos: evidence for coordinate activation of multiple intrinsic cell-cycle checkpoints at the mid-blastula transition

Zygote ◽  
1997 ◽  
Vol 5 (2) ◽  
pp. 153-175 ◽  
Author(s):  
Richard Ikegami ◽  
Alma K. Rivera-Bennetts ◽  
Deborah L. Brooker ◽  
Thomas D. Yager
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Adaptive Response ◽  
Topoisomerase I ◽  
Topoisomerase Ii ◽  
Cell Cycle Checkpoints ◽  
Zebrafish Embryos ◽  
Replication Process ◽  
Inhibition Of Dna Synthesis

SummaryWe address the developmental activation, in the zebrafish embryo, of intrinsic cell-cycle checkpoints which monitor the DNA replication process and progression through the cell cycle. Eukaryotic DNA replication is probably carried out by a multiprotein complex containing numerous enzymes and accessory factors that act in concert to effect processive DNA synthesis (Applegren, N. et al. (1995) J. Cell. Biochem. 59, 91–107). We have exposed early zebrafish embryos to three chemical agents which are predicted to specifically inhibit the DNA polymerase α, topoisomerase I and topoisomerase II components of the DNA replication complex. We present four findings: (1) Before mid-blastula transition (MBT) an inhibition of DNA synthesis does not block cells from attempting to proceed through mitosis, implying the lack of functional checkpoints. (2) After MBT, the embryo displays two distinct modes of intrinsic checkpoint operation. One mode is a rapid and complete stop of cell division, and the other is an ‘adaptive’ response in which the cell cycle continues to operate, perhaps in a ‘repair’ mode, to generate daughter nuclei with few visible defects. (3) The embryo does not display a maximal capability for the ‘adaptive’ response until several hours after MBT, which is consistent with a slow rranscriptional control mechanism for checkpoint activation. (4) The slow activation of checkpoints at MBT provides a window of time during which inhibitors of DNA synthesis will induce cytogenetic lesions without killing the embryo. This could be useful in the design of a deletion-mutagenesis strategy.

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.

scholarly journals Amphibian Lens Histones and Their Relation to the Cell Cycle

1970 ◽  
Vol 55 (5) ◽  
pp. 688-702 ◽  
Author(s):  
Alan Johnson ◽  
Howard Rothstein
Keyword(s):  
Cell Cycle ◽  
Epithelial Cells ◽  
Dna Synthesis ◽  
Tissue Specific ◽  
Fiber Cells ◽  
Early Stages ◽  
Histone Synthesis ◽  
Inhibition Of Dna Synthesis ◽  
First Time ◽  
Amphibian Lens

Histones have been electrophoretically separated from acid extracts of the frog lens for the first time. The five conventional histone fractions, representing four electrophoretic bands (f1; f2b, f3; f2a2; and f2a1), are present in both the epithelial and fiber cells. In addition, a fifth fraction was isolated from both sources and the evidence suggests that it may be a tissue-specific histone, possibly related to the lysine-rich f2c fraction found previously only in nucleated erythrocytes. The epithelial cells contain a substantially greater amount of histone than the fiber cells. Moreover, the fibers, unlike the epithelium, manifest no net histone synthesis or turnover following lenticular explantation. Microspectrophotometric, radioautographic, and gel electrophoretic studies indicate that the histones are synthesized in frog lenses concurrently with DNA. Inhibition of DNA synthesis does not completely abolish that of histones but reduces it by about one-half. In the early stages of culture (prior to their synthesis and that of DNA) the histones appear to undergo alterations which are prevented by treatment with cycloheximide.

scholarly journals Intracellular free Ca2+ in the cell cycle in human fibroblasts: transitions between G1 and G0 and progression into S phase.

1993 ◽  
Vol 4 (3) ◽  
pp. 293-302 ◽  
Author(s):  
M Wahl ◽  
E Gruenstein
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Dose Response ◽  
Human Fibroblasts ◽  
S Phase ◽  
Free Calcium ◽  
Response Curves ◽  
Serum Stimulation ◽  
Inhibition Of Dna Synthesis ◽  
Stimulation Of

Intracellular free calcium ([Ca2+]i) has been proposed to play an important part in the regulation of the cell cycle. Although a number of studies have shown that stimulation of quiescent cells with growth factors causes an immediate rise in [Ca2+]i (Rabinovitch et al., 1986; Vincentini and Villereal, 1986; Hesketh et al., 1988; Tucker et al., 1989, Wahl et al., 1990), a causal relationship between the [Ca2+]i transient and the ability of the cells to reenter the cell cycle has not been firmly established. We have found that blocking the mitogen-induced elevation of [Ca2+]i with the cytoplasmic [Ca2+]i buffer dimethyl BAPTA (dmBAPTA) also blocks subsequent entry of cells into S phase. The dose response curves for inhibition of serum stimulation of [Ca2+]i and DNA synthesis by dmBAPTA are virtually identical including an anomalous stimulation observed at low levels of dmBAPTA. Reversal of the [Ca2+]i buffering effect of dmBAPTA by transient exposure of the cells to the Ca2+ ionophore ionomycin also reverses the inhibition of DNA synthesis 20-24 h later. Ionomycin by itself does not stimulate DNA synthesis. These data are consistent with the conclusion that a transient increase in [Ca2+]i occurring shortly after serum stimulation of quiescent fibroblasts is necessary but not sufficient for subsequent entry of the cells into S phase. This study is the first to show a direct relationship between early serum stimulated Cai2+ increase and subsequent DNA synthesis in human cells. It also goes beyond recent studies on BALB/3T3 cells by providing dose response data and demonstrating reversibility, which are strong indications of a cause and effect relationship.

Relationship between nucleoside triphosphate pools and DNA replication in the cell cycle of Escherichia coli

1974 ◽  
Vol 20 (5) ◽  
pp. 747-750 ◽  
Author(s):  
George G. Khachatourians ◽  
Lydia Huzyk
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Dna Replication ◽  
Dna Synthesis ◽  
Specific Inhibitor ◽  
Replication Cycle ◽  
Nucleoside Triphosphate ◽  
E Coli ◽  
Synchronous Cultures ◽  
Inhibition Of Dna Synthesis

The correlation between DNA replication and the nucleoside triphosphate pool fluctuation in the cell cycle of Escherichia coli B/r was examined. 32P-labelled endogenous nucleoside triphosphates in normal synchronous cultures of E. coli B/r and those in which the chromosome replication cycle was inhibited by nalidixic acid, a specific inhibitor of DNA synthesis, were compared. No marked accumulation or depletion of nucleoside triphosphate pools was observed during the inhibition of DNA synthesis in the cell cycle. We suggest that changes in the pool levels during the cell cycle of E. coli occur independently of the DNA replication cycle.

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