Radiation and the G 2 Phase of the Cell Cycle

Hwang, Arlene; Muschel, Ruth J.

doi:10.2307/3579808

Cited by 83 publications

(51 citation statements)

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“…26,27 Furthermore, it has been largely reported that this G2 checkpoint is particularly important in preventing mitotic catastrophe in cells exposed to DNA damage (for a review, See Roninson et al 8 ). We therefore compared the effect of expressing either RhoB-F or RhoB-GG on radiation-induced G2/M arrest.…”

Section: Rhob-f Cells Displayed An Increased G2 Arrest Following Irramentioning

confidence: 99%

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication

et al. 2005

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Our previous results demonstrated that expressing the GTPase ras homolog gene family, member B (RhoB) in radiosensitive NIH3T3 cells increases their survival following 2 Gy irradiation (SF2). We have first demonstrated here that RhoB expression inhibits radiation-induced mitotic cell death. RhoB is present in both a farnesylated and a geranylgeranylated form in vivo. By expressing RhoB mutants encoding for farnesylated (RhoB-F cells), geranylgeranylated or the CAAX deleted form of RhoB, we have then shown that only RhoB-F expression was able to increase the SF2 value by reducing the sensitivity of these cells to radiation-induced mitotic cell death. Moreover, RhoB-F cells showed an increased G2 arrest and an inhibition of centrosome overduplication following irradiation mediated by the Rhokinase, strongly suggesting that RhoB-F may control centrosome overduplication during the G2 arrest after irradiation. Overall, our results for the first time clearly implicate farnesylated RhoB as a crucial protein in mediating cellular resistance to radiation-induced nonapoptotic cell death.

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Section: Rhob-f Cells Displayed An Increased G2 Arrest Following Irramentioning

confidence: 99%

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication

et al. 2005

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“…Potential targets of UCN-01 are currently under much investigation and it is suggested to act specifically at the G2/M transition. Cell cycle arrest at G2 is tightly controlled by a series of phosphorylation reactions (reviewed in Hwang and Muschel, 1998;Russell, 1998). In short, IR induces a G2 arrest through inactivation of the cyclin B/Cdc2 complex.…”

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Abrogation of the radiation-induced G2 checkpoint by the staurosporine derivative UCN-01 is associated with radiosensitisation in a subset of colorectal tumour cell lines

et al. 2002

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Ionising radiation is commonly used in the treatment of colorectal cancer. Tumour cells with mutant p53 undergo cell cycle arrest at G2/M after ionising radiation and evidence suggests that abrogation of this G2 arrest can lead to a premature, aberrant mitosis, thus enhancing ionising radiation-induced cell killing. The G2 checkpoint inhibitor UCN-01 was thus investigated to determine whether it would abrogate the G2 checkpoint induced by 5 Gy ionising radiation in a range of colorectal tumour cell lines. Data presented show that, at doses that are alone non-toxic to the cells, UCN-01 inhibits the ionising radiation-induced G2 checkpoint in five colorectal tumour cell lines with mutant p53. The ability of UCN-01 to sensitise cells to ionising radiation-induced growth inhibition and apoptosis was also investigated and UCN-01 was found to radiosensitise two out of five cell lines. These results were confirmed by long-term colony forming efficiency studies. These results demonstrate that abrogation of the ionising radiation-induced G2 checkpoint is not necessarily associated with sensitisation to ionising radiation, however, some colorectal tumour cell lines can be radiosensitised by UCN-01. Although the mechanism of radiosensitisation is not clear, this may still be an important treatment strategy.

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“…[3][4][5][6][7] The mechanisms of G2 arrest in contrast have been described to a lesser extent, although this event could be of relevance to the cellular survival after photonirradiation. 8,9 Beyond doubt, the G2-phase arrest is generally activated in response to DNA damage independent of the p53 status. 8 It acts as an universal feedback for maintaining the genomic integrity and for survival after irradiation by repairing DNA breaks prior to mitosis.…”

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confidence: 99%

“…8,9 Beyond doubt, the G2-phase arrest is generally activated in response to DNA damage independent of the p53 status. 8 It acts as an universal feedback for maintaining the genomic integrity and for survival after irradiation by repairing DNA breaks prior to mitosis. 10 Much of the underlying knowledge on the G2/M phase was obtained by studying genes involved in the regulation of DNA damage response because DNA-damaging processes, like g-radiation, respond by arresting at cell cycle checkpoints.…”

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confidence: 99%

“…11 This ''G2 delay'' after photon-irradiation involves molecular mechanisms like reduced cyclin B levels and inhibition of the Cdk1 activity. 8 Formation and activation of the maturation promoting factor (MPF) are pivotal for the G2/M checkpoint regulation. The transition from G2 into the mitosis occurs by the activation of the MPF harboring the serine threonine cyclin-dependent protein kinase p34 cdc2 , which is controlled by the p34 cdc2 /cyclin B1 complex formation.…”

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confidence: 99%

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Induced and repressed genes after irradiation sensitizing by pentoxyphylline

Waldeck

Strunz

Müller

et al. 2006

Intl Journal of Cancer

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Aim in cancer therapy is to increase the therapeutic ratio eliminating the disease while minimizing toxicity to normal tissues. Radiation therapy is a main component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX) have been evaluated to improve radiotherapy. Commonly, cells respond to radiation by the activation of specific early and late response genes as well as by inhibition of genes, which are expressed under normal conditions. A display of the genetic distinctions at the level of transcription is given here to characterize the molecular events underlying the radiosensitizing mechanisms. The method of suppression subtractive hybridization allows the visualization of both induced and repressed genes in irradiated cells compared with cells sensitized immediately after irradiation. The genes were isolated by cDNA-cloning, differential analysis and sequence similarity search. Genes involved in protein synthesis, metabolism, proteolysis and transcriptional regulation were detected. It is important that genes like KIAA280, which were only known as unidentified EST sequences before without function, but inaccessible by array technology were recovered as functional genes. Database searches for PTX-induced genes detected a human mRNA completely unknown. In case of suppressed genes, we detected several mRNAs; one thereof shows homology to a hypothetical protein possibly involved in signal transduction. A further mRNA encodes the protein BM036 supposed to associate with the E2F transcription factor. A hypothetical protein H41 was detected, which may repress the Her-2/neu receptor influencing breast cancer, gliomas and prostate tumors. Radiation combined with PTX may lead to a better prognosis by down regulation of the Her-2/neu, which will be proven by clinical studies in the near future. The connection between cancerogenesis and cyclins has been demonstrated with the aberrant expression of members of the family of cyclins and the mechanisms of the cell cycle G1 arrest and apoptosis were well documented. [3][4][5][6][7] The mechanisms of G2 arrest in contrast have been described to a lesser extent, although this event could be of relevance to the cellular survival after photonirradiation. 8,9 Beyond doubt, the G2-phase arrest is generally activated in response to DNA damage independent of the p53 status. 8 It acts as an universal feedback for maintaining the genomic integrity and for survival after irradiation by repairing DNA breaks prior to mitosis. 10 Much of the underlying knowledge on the G2/M phase was obtained by studying genes involved in the regulation of DNA damage response because DNA-damaging processes, like g-radiation, respond by arresting at cell cycle checkpoints. 11 This ''G2 delay'' after photon-irradiation involves molecular mechanisms like reduced cyclin B levels and inhibition of the Cdk1 activity. 8 Formation and activation of the maturation promoting factor (MPF) are pivotal for the G2/M checkpoint regulation. The transition from G2 into the mitosis occurs by the activatio...

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Radiation and the G 2 Phase of the Cell Cycle

Cited by 83 publications

References 90 publications

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication

Farnesylated RhoB inhibits radiation-induced mitotic cell death and controls radiation-induced centrosome overduplication

Abrogation of the radiation-induced G2 checkpoint by the staurosporine derivative UCN-01 is associated with radiosensitisation in a subset of colorectal tumour cell lines

Induced and repressed genes after irradiation sensitizing by pentoxyphylline

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