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Results for “G2 Phase”

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At least 19 recordsLinked to original sources

PubMed1999

A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay.

Cyclin D-Cdk4 complexes have a demonstrated role in G1 phase, regulating the function of the retinoblastoma susceptibility gene product (Rb). Previously, we have shown that following treatment with low doses of UV radiation, cell lines that express wild-type p16 and Cdk4 responded with a G2 phase cell cycle delay. The UV-responsive lines contained elevated levels of p16 post-treatment, and the accumulation of p16 correlated with the G2 delay. Here we report that in UV-irradiated HeLa and A2058 cells, p16 bound Cdk4 and Cdk6 complexes with increased avidity and inhibited a cyclin D3-Cdk4 complex normally activated in late S/early G2 phase. Activation of this complex was correlated with the caffeine-induced release from the UV-induced G2 delay and a decrease in the level of p16 bound to Cdk4. Finally, overexpression of a dominant-negative mutant of Cdk4 blocked cells in G2 phase. These data indicate that the cyclin D3-Cdk4 activity is necessary for cell cycle progression through G2 phase into mitosis and that the increased binding of p16 blocks this activity and G2 phase progression after UV exposure.

Cyclin D↗

PubMed2001

Novel findings regarding photoinduced commitments of G1-, S- and G2-phase cells to cell-cycle transitions in darkness and dark-induced G1-, S- and G2-phase arrests in Euglena.

Effects of light and darkness on cell-cycle progression were studied in the log-linear photoautotrophic growth mode of Euglena gracilis. We found that there are light-dependent restriction points in the post-G1 phases, quite in contrast to Chlamydomonas, where a light-dependent restriction is known to exist only in the G1 phase. Thus, in E. gracilis, there are photoinduced commitments of G1-, S- and G2-phase cells that allow them to progress to the G1, S and G2 phases in darkness, and there are dark-induced G1-, S- and G2-phase arrests. In darkness, only committed cells were able to progress to the committed phases (G1, S or G2), whereas uncommitted cells were unable to undergo a cell-cycle transition. Whether or not cells were induced to commit by irradiation, they were eventually arrested somewhere in the G1, S or G2 (but not M) phase within 14 h of being transferred to darkness. We also describe the dependence of photoinduced commitment on light intensity and discuss the results as they relate to cell-cycle progression in continuous light.

Animals↗

PubMed2002

Post-transcriptional regulation of cyclin D1 expression during G2 phase.

During continuous proliferation, cyclin D1 protein is induced to high levels in a Ras-dependent manner as cells progress from S phase to G2 phase. To understand the mechanism of the Ras-dependent cyclin D1 induction, cyclin D1 mRNA levels were determined by quantitative image analysis following fluorescent in situ hybridization. Although a slight increase in mRNA expression levels was detected during the S/G2 transition, this increase could not explain the more robust induction of cyclin D1 protein levels. This suggested the involvement of post-transcriptional regulation as a mechanism of cyclin D1 protein induction. To directly test this hypothesis, the cyclin D1 transcription rate was determined by run-on assays. The transcription rate of cyclin D1 stayed steady during the synchronous transition from S the G2 phase. We further demonstrated that cyclin D1 protein levels could increase during G2 phase in the absence of new mRNA synthesis. alpha-Amanitin, a transcription inhibitor, did not suppress cyclin D1 protein elevation as the cells progressed from S to G2 phase, even though the inhibitor was able to completely block cyclin D1 protein induction during reentry into the cell cycle from quiescence. The half life of cyclin D1 protein was shortest during S phase indicating that a change in protein stability might play a role in post-translational induction of cyclin D1 in G2 phase. These data indicate a fundamental difference in the regulation of cyclin D1 production during continuous cell cycle progression and re-initiation of the cell cycle.

Amanitins↗

PubMed1984

S-phase, G2, and nuclear division mutants of Aspergillus nidulans.

Twenty-two temperature-sensitive cell cycle mutants of the fungus Aspergillus nidulans, which block in interphase at restrictive temperature, were analyzed by the reciprocal shift method of Jarvik and Botstein (Proc. Nath Acad. Sci. U.S.A. 70:2046-2050, 1973) and Hereford and Hartwell (J. Mol. Biol. 84:445-461, 1974) to determine whether these mutations were blocked at the G1, S, or G2 phase of the cell cycle. We found five mutants to be blocked in S and nine to be blocked in G2. Two of the G2 mutants were atypical in that they were not able to accomplish the G2 to M transition at restrictive temperature but nevertheless could initiate subsequent cycles of DNA replication. None was blocked in G1. There were nine strains that could not be classified. The block imposed by restrictive temperature was irreversible in three of these strains, and the six other strains were unclassifiable due to their aberrant terminal nuclear phenotypes.

Aspergillus nidulans↗

PubMed1991

The effect of cryopreservation on the development of S- and G2-phase mouse embryos.

The survival rate and development of four-cell-stage mouse embryos frozen and thawed in S phase versus G2 phase was compared. Significantly more G2-phase than S-phase embryos survived freezing and thawing. In both groups, disruption of the zona pellucida, fusion of blastomeres, and dispersion of chromosomes were occasionally observed after thawing. Cryopreservation resulted in a longer delay in cleavage from the four- to the eight-cell stage of S (about 5 hr)- and G2-phase embryos (about 3 hr) compared to unfrozen controls. The number of frozen embryos which developed to the blastocyst stage was reduced compared to controls, and in the case of S-phase embryos, formation of the blastocyst cavity was also delayed. However, the average number of cells in the experimental and control embryos was similar. No increased incidence of chromosome abnormalities was seen. Our results suggest that freezing embryos in G2 is superior to freezing in S phase.

Animals↗

PubMed1996

Okadaic acid overrides the S-phase check point and accelerates progression of G2-phase to induce premature mitosis in HeLa cells.

Okadaic acid has been shown to induce premature mitosis in HeLa cells belonging to both S-phase and G2-phase. The response is dependent on concentration and perhaps also on the differential susceptibility of cells to okadaic acid (OA). OA resembles caffeine in its ability to override the DNA-replication check point but differs in being capable of inducing premature mitosis in cells in G2-phase, thereby accelerating mitosis. Chromosomes from mitotic cells induced in G2-phase show a typical banding pattern similar to G-banding. From immunoblot experiments and survey of the relevant literature it has been argued that OA may modulate both a tyrosine kinase and a tyrosine phosphatase activity to override the S-phase checkpoint and accelerate the activation of MPF in cells in G2-phase, respectively.

Cell Cycle↗

PubMed1981

Nascent replicons are synchronously joined at the end of S phase or during G2 phase in peas.

In synchronized meristematic cells of Pisum sativum replicon-size DNA-fragments ((14--27) . 10(6) daltons) are not joined until the cells achieve a 4C DNA content. The combined use of a pulse-chase labeling protocol, single-cell autoradiography, cytophotometry, and velocity sedimentation in alkaline sucrose gradients showed that, unlike low molecular weight DNA (i.e., Okazaki fragments) which is ligated soon after replication starts, the joining of nascent replicon-size DNA is delayed until G2. In addition, this observation argues for the existence of replicon termini, although the data are insufficient to determine the true nature of these termini, i.e., whether they are coded in the DNA itself or simply arise as a consequence of the convergence of two replicating forks.

Cell Cycle↗

PubMed2001

Cdc25-dependent activation of cyclin A/cdk2 is blocked in G2 phase arrested cells independently of ATM/ATR.

Cyclin A/cdk2 is active during S and G2 phases of the cell cycle, but its regulation and function during G2 phase is poorly understood. In this study we have examined the regulation of cyclin A/cdk2 activity during normal G2 phase progression and in genotoxin-induced G2 arrest. We show that cyclin A/cdk2 is activated in early G2 phase by a cdc25 activity. In the G2 phase checkpoint arrest initiated in response to various forms of DNA damage, the cdc25-dependent activation of both cyclin A/cdk2 and cyclin B1/cdc2 is blocked. Ectopic expression of cdc25B, but not cdc25C, in G2 phase arrested cells efficiently activated both cyclin A/cdk2 and cyclin B1/cdc2. Finally, we demonstrate that the block in cyclin A/cdk2 activation in the G2 checkpoint arrest is independent of ATM/ATR. We speculate that the ATM/ATR-independent block in G2 phase cyclin A/cdk2 activation may act as a further layer of checkpoint control, and that blocking G2 phase cyclin A/cdk2 activation contributes to the G2 phase checkpoint arrest.

Ataxia Telangiectasia Mutated Proteins↗

PubMed1988

Effect of caffeine in Fanconi anemia. I. Restoration of a normal duration of G2 phase.

In Fanconi anemia (FA) cells the duration of the G2 phase of the cell cycle prolonged. Such a slowing of the G2 phase can be induced in normal cells by irradiation with gamma rays during S phase, which also further increases the duration of G2 in FA cells. The addition of caffeine during the last 7 h of culture shortens the G2 phase in both nonirradiated and irradiated FA cells. In nonirradiated normal cells it may have no effect or may increase G2 phase duration, but in irradiated normal reduces the slowing of G2 induced by the radiation. This suggests that FA cells recognize and repair preexisting DNA lesions during G2 phase and that caffeine inhibits this process. The principal anomaly in FA may be a deficient repair during S phase, as manifest in the prolonged postreplication repair period during G2 phase required to repair the larger number of lesions passing through S phase.

Anemia, Aplastic↗

PubMedDate not supplied

DNA damage responses in cell cycle G2 phase and mitosis--tracking and targeting.

BACKGROUND: In order to determine temporal responses of cell cycle populations to DNA damage, a rational combination of cell cycle analyses is critical. Moreover, the targeting of cell cycle checkpoint responses may modify the cytotoxic effect of DNA damage. MATERIALS AND METHODS: The characteristics of cell cycle populations (DNA content, cell cycle transitioning of S phase cells and size of mitotic cell fraction within the total G2/M phase population) in HeLa cells exposed to ionizing radiation were analyzed using three individual flow cytometry-based assays. The potential radiosensitization from inhibiting DNA damage responses was assessed by the colony formation assay. RESULTS: Irradiation resulted in an initial accumulation of S phase cells in G2 phase, from which the arrested cells were subsequently released to enter mitosis. Upon drug inhibition of G2 checkpoint signaling or mitotic progression, the cytotoxic effect of ionizing radiation on the HeLa cells was amplified. CONCLUSION: DNA damage-induced cell cycle responses, analyzed by selected cytometry assays and modified by specific targeting, might contribute to an understanding of how to improve radiotherapy outcome.

Cell Division↗

PubMed2004

Peplomycin induces G1-phase specific apoptosis in liver carcinoma cell line Bel-7402 involving G2-phase arrest.

AIM: To investigate the mechanism of peplomycin (PEP)-induced apoptosis in liver carcinoma cell line (Bel-7402). METHODS: Growth inhibition by PEP was analyzed using 3- 4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptotic cells were detected using Hoechest 33258 staining, and confirmed by flow cytometric analysis and DNA fragmentation analysis. The expression of cyclin A and B1 were determined by flow cytometry and Western blot. Annexin V assay was measured by flow cytometric analysis. RESULTS: PEP induced apoptosis and then inhibited cell proliferation in liver carcinoma cell line Bel-7402. Cells treated with PEP 50 mumol/L for 15 h were arrested in G2-phase with dramatical expression of cyclin A and a little change in cyclin B1. Almost all the apoptosis occurred in cells undergoing the G1-phase after treatment for 24 h. CONCLUSION: Peplomycin induced G1-phase specific apoptosis in Bel-7402 involving G2-phase arrest.

Antibiotics, Antineoplastic↗

PubMed1996

Attenuation of G2-phase cell cycle checkpoint control is associated with increased frequencies of unrejoined chromosome breaks in human tumor cells.

To test the hypothesis that attenuation in G2-phase checkpoint control leads to elevated frequencies of unrejoined chromosome breaks in mitosis, the relationship between G2-phase cell cycle checkpoint control and unrejoined chromosome break frequencies after radiation exposure was examined in cells of 10 human tumor cell lines: 8 squamous cell carcinoma cell lines and 2 lymphoblastoid cell lines. Most of the delay in progression through the cell cycle seen in the first cell cycle after radiation exposure in these cell lines was due to blocks in G2 phase, and there were large cell line-dependent variations in the length of the G2-phase block. There was a highly significant inverse correlation between the length of G2-phase delay after radiation exposure and the frequency of induced unrejoined chromosome breaks seen as chromosome terminal deletions in mitosis. This observation supports the hypothesis that the signal for G2-phase delay in mammalian cells is an unrejoined chromosome break and that attenuation of G2-phase checkpoint control allows cells with unrejoined breaks to progress into mitosis. Attenuation in G2-phase checkpoint control was not associated with alterations in the frequency of induced chromosome rearrangements, suggesting that most chromosome rearrangements develop prior to G2 phase, and there was no significant relationship between the length of G2-phase delay and inherent radiation sensitivity, suggesting that unrejoined chromosome breaks are not the primary toxic lesion induced by radiation in mammalian cells.

Chromosome Aberrations↗

PubMed1991

After X-irradiation a transient arrest of L929 cells in G2-phase coincides with a rapid elevation of the level of O6-alkylguanine-DNA alkyltransferase.

Following X-irradiation of exponentially growing L929 cells two major phenomena have been observed. First, there was a delay in cell division which can be ascribed to the arrest of cells in the G2-phase (G2-block), and, second, the cellular content of the O6-alkylguanine-DNA alkyltransferase (AGT) was markedly increased. Flow cytometrical DNA-measurements revealed that cells began to accumulate in the G2-phase 4 h after irradiation (p.r.) irrespective of the X-ray dose, while both the fraction of cells blocked in G2 and the time period the cells persisted in G2 increased with the radiation dose. About 24 h past release from the G2-block the distribution of cells in the cell cycle was similar to that of untreated control cells. In comparison with control cells the AGT content in irradiated cells (4 Gy) was highest at about 48 h p.r. (3.4-fold increase). The highest ratio of increase in AGT was, however, observed to occur between about 4 and 13 h p.r. (2.6-fold increase). As shown by flow cytometrical measurements using a BrdUrd/DNA double labeling technique, this rapid primary increase in AGT coincides very well with the entrance of cells into the G2-phase. This indicates that the cellular AGT content in X-irradiated (parental) cells started to exceed the basal level at the beginning of the G2-phase, but not before or during the S-phase. Once the AGT level was elevated it continued to increase for 2 to 3 cell doubling times.

Animals↗

PubMed1994

Modulation of the spontaneous G2 phase blockage in Fanconi anemia cells by caffeine: differences from cells arrested by X-irradiation.

The effect of caffeine on the endogenous G2 phase cell cycle blockage of Fanconi anemia (FA) cells was compared with the effect of caffeine on the G2 phase blockage induced in control cells by X-irradiation. The G2 phase accumulations in FA cells could be completely resolved by exposure to 1.5 mM caffeine. This was also observed in three brothers with endogenous G2 phase blockage due to unusual BrdU sensitivity. In contrast, G2 phase blockage induced by X-irradiation was only partially resolved by exposure to caffeine. The rescued G2 phase cells from FA patients were arrested within the following G1 phase compartments. This was not seen in X-irradiated cells from control donors. These results point towards a different nature and/or repair mechanism of the endogenous G2 phase lesion in FA cells compared to that induced by X-irradiation in control cells.

Caffeine↗

PubMed2002

Caffeine eliminates gamma-ray-induced G2-phase delay in human tumor cells but not in normal cells.

It has been known for many years that caffeine reduces or eliminates the G2-phase cell cycle delay normally seen in human HeLa cells or Chinese hamster ovary (CHO) cells after exposure to X or gamma rays. In light of our recent demonstration of a consistent difference between human normal and tumor cells in a G2-phase checkpoint response in the presence of microtubule-active drugs, we examined the effect of caffeine on the G2-phase delays after exposure to gamma rays for cells of three human normal cell lines (GM2149, GM4626, AG1522) and three human tumor cell lines (HeLa, MCF7, OVGI). The G2-phase delays after a dose of 1 Gy were similar for all six cell lines. In agreement with the above-mentioned reports for HeLa and CHO cells, we also observed that the G2-phase delays were eliminated by caffeine in the tumor cell lines. In sharp contrast, caffeine did not eliminate or even reduce the gamma-ray-induced G2-phase delays in any of the human normal cell lines. Since caffeine has several effects in cells, including the inhibition of cAMP and cGMP phosphodiesterases, as well as causing a release of Ca(++) from intracellular stores, we evaluated the effects of other drugs affecting these processes on radiation-induced G2-phase delays in the tumor cell lines. Drugs that inhibit cAMP or cGMP phosphodiesterases did not eliminate the radiation-induced G2-phase delay either separately or in combination. The ability of caffeine to eliminate radiation-induced G2-phase delay was, however, partially reduced by ryanodine and eliminated by thapsigargin, both of which can modulate intracellular calcium, but by different mechanisms. To determine if caffeine was acting through the release of calcium from intracellular stores, calcium was monitored in living cells using a fluorescent calcium indicator, furaII, before and after the addition of caffeine. No calcium release was seen after the addition of caffeine in either OVGI tumor cells or GM2149 normal cells, even though a large calcium release was measured in parallel experiments with ciliary neurons. Thus it is likely that caffeine is eliminating the radiation-induced G2-phase delay through a Ca(++)-independent mechanism, such as the inhibition of a cell cycle-regulating kinase.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2001

Rejoining of isochromatid breaks induced by heavy ions in G2-phase normal human fibroblasts.

We reported previously that exposure of normal human fibroblasts in G2 phase of the cell cycle to high-LET radiation produces a much higher frequency of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G2-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in normal G2-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucleon), silicon (490 MeV/nucleon), or iron (200 MeV/nucleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirradiation incubation times ranging from 0 to 600 min. Chromosomes were stained with Giemsa, and aberrations were scored in cells at G2 phase. G2-phase fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after exposure to 440 keV/microm iron particles, probably due to isochromatid-isochromatid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isochromatid-isochromatid exchanges cannot be detected. Increased induction of isochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radiation.

Cells, Cultured↗

PubMedDate not supplied

[The nature of the lengthening of the G2 phase in the mitotic cycle of parenchymal cells of the mouse liver].

The phenomenon of G2 phase prolongation was found in the population of mouse hepatocytes. In normal postnatal liver growth, G2 phase prolongation in not pronounced and occurs in a small fraction of proliferating hepatocytes. In case of liver regeneration after removal of 2/3 of the organ, G2 phase prolongation is observed in a population of hepatocytes, which response to the proliferative stimulus first. Estimation of individual variation in expression of prolonged G2 phase along with the detailed analysis of the structure of the process of proliferation in the main population of hepatocytes (cells with normal G2 phase) allows to define the biological meaning of the "G2-population" observed. The prolongation of G2 phase may result from non-specific cell damage in mitotic cycles, caused by destruction of trophic relations in liver during its growth and regeneration.

Aging↗

PubMed2003

An association between the radiation-induced arrest of G2-phase cells and low-dose hyper-radiosensitivity: a plausible underlying mechanism?

The survival of asynchronous and highly enriched G1-, S- and G2-phase populations of Chinese hamster V79 cells was measured after irradiation with 60Co gamma rays (0.1-10 Gy) using a precise flow cytometry-based clonogenic survival assay. The high-dose survival responses demonstrated a conventional relationship, with G2-phase cells being the most radiosensitive and S-phase cells the most radioresistant. Below 1 Gy, distinct low-dose hyper-radiosensitivity (HRS) responses were observed for the asynchronous and G2-phase enriched cell populations, with no evidence of HRS in the G1- and S-phase populations. Modeling supports the conclusion that HRS in asynchronous V79 populations is explained entirely by the HRS response of G2-phase cells. An association was discovered between the occurrence of HRS and the induction of a novel G2-phase arrest checkpoint that is specific for cells that are in the G2 phase of the cell cycle at the time of irradiation. Human T98G cells and hamster V79 cells, which both exhibit HRS in asynchronous cultures, failed to arrest the entry into mitosis of damaged G2-phase cells at doses less than 30 cGy, as determined by the flow cytometric assessment of the phosphorylation of histone H3, an established indicator of mitosis. In contrast, human U373 cells that do not show HRS induced this G2-phase checkpoint in a dose-independent manner. These data suggest that HRS may be a consequence of radiation-damaged G2-phase cells prematurely entering mitosis.

Animals↗