Reduced inhibition of DNA synthesis and G2 arrest during the cell cycle of resistant HeLa cells in response tocis-diamminedichloroplatinum

1994 ◽  
Vol 1 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Sue Lin-Chao ◽  
Chuck C. K. Chao
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Hela Cells ◽  
G2 Arrest ◽  
Inhibition Of Dna Synthesis

Replication and transcription sites are colocalized in human cells

1994 ◽  
Vol 107 (2) ◽  
pp. 425-434 ◽  
Author(s):  
A.B. Hassan ◽  
R.J. Errington ◽  
N.S. White ◽  
D.A. Jackson ◽  
P.R. Cook
Keyword(s):  
Cell Cycle ◽  
Confocal Microscopy ◽  
Dna Synthesis ◽  
Fluorescent Probes ◽  
Hela Cells ◽  
Nuclear Architecture ◽  
Human Cells ◽  
Dynamic Nature ◽  
Nucleotide Triphosphates ◽  
Transcription Sites

HeLa cells synchronized at different stages of the cell cycle were permeabilized and incubated with analogues of nucleotide triphosphates; then sites of incorporation were immunolabeled with the appropriate fluorescent probes. Confocal microscopy showed that sites of replication and transcription were not diffusely spread throughout nuclei, reflecting the distribution of euchromatin; rather, they were concentrated in ‘foci’ where many polymerases act together. Transcription foci aggregated as cells progressed towards the G1/S boundary; later they dispersed and became more diffuse. Replication was initiated only at transcription sites; later, when heterochromatin was replicated in enlarged foci, these remained sites of transcription. This illustrates the dynamic nature of nuclear architecture and suggests that transcription may be required for the initiation of DNA synthesis.

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.

Changes in the organization of chromosomes during the cell cycle: response to ultraviolet light

1975 ◽  
Vol 17 (3) ◽  
pp. 539-565
Author(s):  
S.L. Schor ◽  
R.T. Johnson ◽  
C.A. Waldren
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Ultraviolet Light ◽  
Hela Cells ◽  
Close Correlation ◽  
Chromosome Condensation ◽  
Unscheduled Dna Synthesis ◽  
Interphase Chromosome ◽  
Interphase Cells ◽  
Chromosome Decondensation

Fusion between mitotic and interphase cells results in the premature condensation of the interphase chromosomes into a morphology related to the position in the cell cycle at the time of fusion. These prematurely condensed chromosomes (PCC) have been used in conjunction with u.v. irradiation to examine the interphase chromosome condensation cycle of HeLa cells. The following observations have been made: (I) There is a progressive decondensation of the chromosomes during G1 which is accentuated by u.v. irradiation: (2) The chromosomes become more resistant to u.v.-induced decondensation during G2 and mitosis. (3) There is a close correlation between the degree of chromosome decondensation and the amount of unscheduled DNA synthesis induced by u.v. irradiation during G1 and mitosis: (4) Hydroxyurea enhances the ability of u.v. irradiation to promote the decondensation of chromosomes during G1, G2 and mitosis. Hydroxyurea also potentiates the lethal action of u.v. irradiation during mitosis and G1. These data are discussed in relation to the suggestion that chromosomes undergo a progressive decondensation during G1 and condensation during G2.

The induction of DNA synthesis in the chick red cell nucleus in heterokaryons during the first cell cycle after fusion with HeLa cells

1975 ◽  
Vol 18 (3) ◽  
pp. 455-490
Author(s):  
R.T. Johnson ◽  
A.M. Mullinger
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Hela Cells ◽  
S Phase ◽  
Red Cells ◽  
Red Cell ◽  
Embryonic Chick ◽  
Cell Cycles ◽  
Phase Protein ◽  
Different Parts

Induction of DNA synthesis in embryonic chick red cells has been examined during the first and second cell cycles after fusion with HeLa cells synchronized in different parts of G1 and S-phase. The data indicate that: (i) the younger the embryonic blood the more rapidly the red cells are induced into DNA synthesis; (ii) the greater the ratio of HeLa to chick nuclei in the heterokaryon, the more rapidly the induction occurs; (iii) DNA synthesis in the chick nucleus can continue after the HeLa nucleus has left S-phase and entered either G2 or mitosis; (iv) the induction potential of late S-phase HeLa is somewhat lower than that of early or mid S-phase cells; (v) less than 10% of the chick DNA is replicated during the first cycle after fusion and only a small proportion (15%) of the chick nuclei approach the 4C value of DNA during the second cycle after fusion; (vi) the newly synthesized DNA is associated either with the condensed regions of the nucleus or with the boundaries between condensed and non-condensed regions; (vii) the chick chromosomes at the first and second mitosis after fusion are in the form of PCC prematurely condensed chromosomes); they are never fully replicated and are often fragmentary; (viii) DNA synthesis in the chick nuclei is accompanied by an influx of protein (both G1 and S-phase protein) from the HeLa component of the heterokaryon.

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