Cyclic AMP and theophylline enhance DNA synthesis in L cells stimulated with anti-actin IgG and [(IgG)2protein A]2 complex by recruiting cells into S-phase

1985 ◽  
Vol 67 (2) ◽  
pp. 135-144 ◽  
Author(s):  
William T. Shearer ◽  
Robert G. Ulrich ◽  
John E. McClure ◽  
Catherine G. Green ◽  
Ellen B. Gilliam ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
S Phase ◽  
L Cells

Effects of adenosine 5′-monophosphate and adenosine 3′,5′-cyclic monophosphate on l cells

1975 ◽  
Vol 19 (2) ◽  
pp. 305-313
Author(s):  
J. Taylor-Papadimitriou ◽  
T. Karemfyllis ◽  
A. Eukarpidou ◽  
G. Karamanlidou
Keyword(s):  
Cyclic Amp ◽  
Adenine Nucleotides ◽  
Inhibitory Effect ◽  
S Phase ◽  
Breakdown Product ◽  
Intracellular Level ◽  
Effective Inhibitor ◽  
Growth Inhibitory Effect ◽  
L Cells ◽  
Growth Inhibitory

The adenine nucleotides, 5′-AMP and 3′,5′-cyclic AMP block L cells in the S-phase of the cell cycle. The intracellular level of cyclic AMP is reduced after incubation of cells with 5′-AMP, and rates of uridine transport are increased after incubation with either 5′-AMP or cyclic AMP. On the contrary, cyclic AMP levels are increased and uridine transport decreased in cells treated with an inhibitor of the cyclic AMP phosphodiesterase. This inhibitor partially reverses the growth-inhibitory effect of cyclic AMP, indicating that a breakdown product is the effective inhibitor of growth. The inhibition of cell growth induced by the adenine nucleotides is prevented by uridine, suggesting that the block in S is due to a lack of availability of pyrimidines.

The Time of Synthesis of Satellite DNA in Mouse Cells (L Cells)

1972 ◽  
Vol 50 (2) ◽  
pp. 229-231 ◽  
Author(s):  
A. K. Cohen ◽  
H. N. Rode ◽  
C. W. Helleiner
Keyword(s):  
Dna Synthesis ◽  
Satellite Dna ◽  
S Phase ◽  
L Cells ◽  
Mouse Cells

In mouse L cells growing in suspension and synchronized with 5-fluorodeoxyuridine, the ratio of the rate of synthesis of satellite DNA to that of major DNA reaches a peak 4 h after the onset of DNA synthesis. Since the duration of the period of DNA synthesis (the S-phase) under these conditions is shortened to about 4 h, the synthesis of satellite DNA occurs late in the S-phase.

Dual effects of glucagon and cyclic amp on dna synthesis in cultured rat hepatocytes: Stimulatory regulation in early G1 and inhibition shortly before the s phase entry

1990 ◽  
Vol 144 (3) ◽  
pp. 523-530 ◽  
Author(s):  
G. Hege Thoresen ◽  
Tor-Erik Sand ◽  
Magne Refsnes ◽  
Olav F. Dajani ◽  
Tormod K. Guren ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Dna Synthesis ◽  
Rat Hepatocytes ◽  
S Phase ◽  
Cultured Rat Hepatocytes ◽  
Phase Entry

scholarly journals Mechanisms of 2′-deoxyguanosine toxicity in mouse T-lymphoma cells with purine nucleoside phosphorylase deficiency and resistance to inhibition of ribonucleotide reductase by dGTP

1990 ◽  
Vol 268 (3) ◽  
pp. 725-731 ◽  
Author(s):  
D S Duan ◽  
T Nagashima ◽  
T Hoshino ◽  
F Waldman ◽  
K Pawlak ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Ribonucleotide Reductase ◽  
Double Mutant ◽  
Purine Nucleoside Phosphorylase ◽  
Feedback Inhibition ◽  
S Phase ◽  
G1 Phase ◽  
Wild Type ◽  
L Cells ◽  
T Lymphoma

Purine nucleoside phosphorylase (PNP; EC 2.4.2.1) deficiency is thought to cause T-lymphocyte depletion by accumulation of dG and dGTP, resulting in feedback inhibition of ribonucleotide reductase (RR; EC 1.17.4.1) and hence DNA synthesis. To test for additional toxic mechanisms of dG, we selected a double mutant of the mouse T-lymphoma S-49 cell line, dGuo-L, which is deficient in PNP and partially resistant to dGTP feedback inhibition of RR. The effects of dG on dGuo-L cells (concn. causing 50% inhibition, IC50 = 150 microM) were compared with those on the wild-type cells (IC50 = 30 microM) and the NSU-1 mutant with PNP deficiency only (IC50 = 15 microM). Fluorescence flow cytometry showed that equitoxic dG concentrations arrested wild-type and NSU-1 cells at the G1-S interface while allowing continued DNA synthesis in the S-phase, whereas the double mutant dGuo-L cells progressed through the cell cycle normally. dGuo-L cells accumulated high levels of dGTP in G1-phase, but not in S-phase cells, because of the utilization of dGTP for DNA synthesis and limited capacity to synthesize dGTP from dG. These results support the hypothesis that dG/dGTP toxicity occurs in the G1-phase or at the G1-S interface. Failure of dG to arrest the double mutant dGuo-L cells at the G1-S interface allows these cells to escape into S-phase, with an accompanying drop in dGTP levels. Thus the partial resistance of dGuo-L cells to dG toxicity may result from their shorter residence time in G1, allowing them to sustain higher dGTP levels. Hence RR inhibition by dGuo may not be the primary toxic mechanism in S-49 cells; rather, it may serve as an accessory event in dG toxicity by keeping the cells in the sensitive phase of the cell cycle. Among the possible targets of dG toxicity is RNA synthesis, which was inhibited at an early stage in dGuo-L cells.

Pronucleus formation, DNA synthesis and metaphase entry in porcine oocytes following intracytoplasmic injection of murine spermatozoa

Zygote ◽  
2003 ◽  
Vol 11 (3) ◽  
pp. 261-270 ◽  
Author(s):  
Bong-Ki Kim ◽  
Sun Hong Cheon ◽  
Youn Jeong Lee ◽  
Sun Ho Choi ◽  
Xiang Shun Cui ◽  
...  
Keyword(s):  
Dna Synthesis ◽  
Normal Cell ◽  
S Phase ◽  
Normal Male ◽  
Ultrastructural Observation ◽  
Intracytoplasmic Injection ◽  
Paternal Factors ◽  
The Mean ◽  
Species Specific ◽  
Mean Time

The onset of pronucleus formation and DNA synthesis in porcine oocytes following the injection of porcine or murine sperm was determined in order to obtain insights into species-specific paternal factors that contribute to fertilisation. Similar frequencies of oocytes with female pronuclei were observed after injection with porcine sperm or with murine sperm. In contrast, male pronuclei formed 8-9 h following the injection of porcine sperm, and 6-8 h following the injection of murine sperm. After pronucleus formation maternally derived microtubules were assembled and appeared to move both male and female pronuclei to the oocyte centre. A few porcine oocytes entered metaphase 22 h after the injection of murine sperm, but normal cell division was not observed. The mean time of onset of S-phase in male pronuclei was 9.7 h following porcine sperm injection and 7.4 h following mouse sperm injection. Ultrastructural observation revealed that male pronuclei derived from murine sperm in porcine oocytes are morphologically similar to normal male pronuclei in porcine zygotes. These results suggest that species-specific paternal factors influence the onset of pronucleus formation and DNA synthesis. However, normal nuclear cytoplasmic interactions were observed in porcine S-phase oocytes following murine sperm injection.

scholarly journals Role of DNA Replication Proteins in Double-Strand Break-Induced Recombination in Saccharomyces cerevisiae

2004 ◽  
Vol 24 (16) ◽  
pp. 6891-6899 ◽  
Author(s):  
Xuan Wang ◽  
Grzegorz Ira ◽  
José Antonio Tercero ◽  
Allyson M. Holmes ◽  
John F. X. Diffley ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Synthesis ◽  
Gene Conversion ◽  
Strand Break ◽  
Double Strand Break ◽  
S Phase ◽  
Temperature Sensitive ◽  
Replication Proteins ◽  
Dna Ligases ◽  
Mcm Proteins

ABSTRACT Mitotic double-strand break (DSB)-induced gene conversion involves new DNA synthesis. We have analyzed the requirement of several essential replication components, the Mcm proteins, Cdc45p, and DNA ligase I, in the DNA synthesis of Saccharomyces cerevisiae MAT switching. In an mcm7-td (temperature-inducible degron) mutant, MAT switching occurred normally when Mcm7p was degraded below the level of detection, suggesting the lack of the Mcm2-7 proteins during gene conversion. A cdc45-td mutant was also able to complete recombination. Surprisingly, even after eliminating both of the identified DNA ligases in yeast, a cdc9-1 dnl4Δ strain was able to complete DSB repair. Previous studies of asynchronous cultures carrying temperature-sensitive alleles of PCNA, DNA polymerase α (Polα), or primase showed that these mutations inhibited MAT switching (A. M. Holmes and J. E. Haber, Cell 96:415-424, 1999). We have reevaluated the roles of these proteins in G2-arrested cells. Whereas PCNA was still essential for MAT switching, neither Polα nor primase was required. These results suggest that arresting cells in S phase using ts alleles of Polα-primase, prior to inducing the DSB, sequesters some other component that is required for repair. We conclude that DNA synthesis during gene conversion is different from S-phase replication, involving only leading-strand polymerization.

scholarly journals A MYBL2 complex for RRM2 transactivation and the synthetic effect of MYBL2 knockdown with WEE1 inhibition against colorectal cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Qian Liu ◽  
Lijuan Guo ◽  
Hongyan Qi ◽  
Meng Lou ◽  
Rui Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Dna Synthesis ◽  
Ectopic Expression ◽  
Building Blocks ◽  
Small Subunit ◽  
S Phase ◽  
Clinical Samples ◽  
Dependent Manner

AbstractRibonucleotide reductase (RR) is a unique enzyme for the reduction of NDPs to dNDPs, the building blocks for DNA synthesis and thus essential for cell proliferation. Pan-cancer profiling studies showed that RRM2, the small subunit M2 of RR, is abnormally overexpressed in multiple types of cancers; however, the underlying regulatory mechanisms in cancers are still unclear. In this study, through searching in cancer-omics databases and immunohistochemistry validation with clinical samples, we showed that the expression of MYBL2, a key oncogenic transcriptional factor, was significantly upregulated correlatively with RRM2 in colorectal cancer (CRC). Ectopic expression and knockdown experiments indicated that MYBL2 was essential for CRC cell proliferation, DNA synthesis, and cell cycle progression in an RRM2-dependent manner. Mechanistically, MYBL2 directly bound to the promoter of RRM2 gene and promoted its transcription during S-phase together with TAF15 and MuvB components. Notably, knockdown of MYBL2 sensitized CRC cells to treatment with MK-1775, a clinical trial drug for inhibition of WEE1, which is involved in a degradation pathway of RRM2. Finally, mouse xenograft experiments showed that the combined suppression of MYBL2 and WEE1 synergistically inhibited CRC growth with a low systemic toxicity in vivo. Therefore, we propose a new regulatory mechanism for RRM2 transcription for CRC proliferation, in which MYBL2 functions by constituting a dynamic S-phase transcription complex following the G1/early S-phase E2Fs complex. Doubly targeting the transcription and degradation machines of RRM2 could produce a synthetic inhibitory effect on RRM2 level with a novel potential for CRC treatment.

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