Control of the G2/M checkpoints after exposure to low doses of ionising radiation: Implications for hyper-radiosensitivity

Fernet, Marie; Mégnin-Chanet, Frédérique; Hall, Janet; Favaudon, Vincent

doi:10.1016/j.dnarep.2009.10.006

Cited by 79 publications

(52 citation statements)

References 37 publications

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“…G 2 /M checkpoint arrest, a crucial endpoint of ATM signaling, coordinates DSB formation and repair with cell cycle pro-gression. The G 2 /M checkpoint has a defined sensitivity and, as a consequence, is not activated by low radiation doses (10,13). The same concept also results in the release of cells from checkpoint arrest prior to completion of DSB repair.…”

mentioning

confidence: 89%

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest

Brunton

Goodarzi

Noon

et al. 2011

Molecular and Cellular Biology

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Heterochromatin (HC) poses a barrier to γH2AX focus expansion and DNA double-strand break (DSB) repair, the latter being relieved by ATM-dependent KAP-1 phosphorylation. Using high-resolution imaging, we show here that the HC superstructure markedly restricts ATM signaling to cell cycle checkpoint proteins. The impact of HC is greater than anticipated from the percentage of HC-DNA and, in distinction to DSB repair, ATM only partly overcomes the constraints posed by HC. Importantly, we examine ATM signaling in human syndromes with disordered HC. After depletion of MeCP2 and DNMT3B, proteins defective in the Rett and immunodeficiency with centromere instability and facial anomalies (ICF) syndromes, respectively, we demonstrate enhanced γH2AX signal expansion at HC-chromocenters in mouse NIH 3T3 cells, which have visible HC-chromocenters. Previous studies have shown that the G 2 /M checkpoint is inefficient requiring multiple DSBs to initiate arrest. MeCP2 and DNMT3B depletion leads to hypersensitive radiation-induced G 2 /M checkpoint arrest despite normal DSB repair. Cell lines from Rett, ICF, and Hutchinson-Guildford progeria syndrome patients similarly showed hyperactivated ATM signaling and hypersensitive and prolonged G 2 /M checkpoint arrest. Collectively, these findings reveal that heterochromatin contributes to the previously described inefficient G 2 /M checkpoint arrest and demonstrate how the signaling response can be uncoupled from DSB repair.

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confidence: 89%

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest

Brunton

Goodarzi

Noon

et al. 2011

Molecular and Cellular Biology

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“…In particular, compound Cdc2(Chk1)-CyclinB involved in the transition from G2 to M is inactivated either by ATM-Chk2-Cdc25 or ATR-Chk1-Cdc25 pathway (48). Gao et al showed that radiation induced considerable DNA damage and apoptosis as measured by the large increase of the percentage of cells with sub-G1 content.…”

Section: Radioprotection At the Cellular Levelmentioning

confidence: 99%

Research progress in the radioprotective effect of superoxide dismutase

et al. 2012

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Irradiation from diverse sources is ubiquitous and closely associated with human activity. Radiation therapy (RT), an important component of the multiple radiation origins, contributes significantly to oncotherapy by killing tumor cells. On the other hand, RT can also cause some undesired normal tissue injuries that afflict numerous cancer patients. Although many promising radioprotective agents are emerging, few of them have entered the market successfully due to various limitations. At present, the most accepted hypothesis for the radiation-caused injury involves reactive oxygen species (ROS) generation. Superoxide dismutase (SOD), the unique enzyme responsible for the dismutation of superoxide radicals, is expected to occupy an indispensable position in the treatment of ROS-mediated tissue injuries originating from exposure to radiation. This review focuses on the mechanism of radioprotection by SOD at the tissue or organ level, cellular level, and molecular level, respectively, in order to provide references for further investigation of radiation injury and development of new radioprotectors.

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“…It has been reported that cells in the G2 and M phases are approximately three times more radiosensitive than cells in the S phase of the cell cycle [3], although the exact mechanism for this phenomenon is unknown. These differences can be therapeutically exploited in chemoradiation through cell cycle redistribution strategies, by using either drugs that arrest cells in radiosensitive G2/M phases or drugs that eliminate radioresistant S phase cells [4]. …”

Section: Introductionmentioning

confidence: 99%

Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

Qian

José

Guo

et al. 2015

Cell Physiol Biochem

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Control of the G2/M checkpoints after exposure to low doses of ionising radiation: Implications for hyper-radiosensitivity

Cited by 79 publications

References 37 publications

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest

Research progress in the radioprotective effect of superoxide dismutase

Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

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Control of the G2/M checkpoints after exposure to low doses of ionising radiation: Implications for hyper-radiosensitivity

Cited by 79 publications

References 37 publications

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G2/M Checkpoint Arrest

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G2/M Checkpoint Arrest

Research progress in the radioprotective effect of superoxide dismutase

Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

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Product

Resources

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Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest

Analysis of Human Syndromes with Disordered Chromatin Reveals the Impact of Heterochromatin on the Efficacy of ATM-Dependent G₂/M Checkpoint Arrest