Double-strand break motions shift radiation risk notions?

Hlatky, Lynn

doi:10.1073/pnas.1118927109

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…The ability to repair DSBs determines the sensitivity of mammalian cells to IR (18,20). The recruitment of several proteins to the damage site is the initial cellular response to DSBs, through which γ-H2AX focus formation is one of the earliest event (19,21). In our study, exogenous TOB1 reduced the amount of γ-H2AX foci induced by IR in the HBE cells (Fig.…”

Section: Discussionsupporting

confidence: 54%

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Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway

Chen

Sun

et al. 2013

Oncology Reports

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The aim of this study was to investigate the effects and mechanisms of antiproliferative transducer of erbB2, 1 (TOB1) on the radiosensitivity of the normal human bronchial epithelial cell line HBE. After exposure to different doses of irradiation or a certain dose for different time intervals, the expression of TOB1 mRNA and protein in HBE cells was determined by semi-quantitative RT-PCR and western blot analysis. Liposome-induced recombinant plasmid transfection and G418 selection were performed to establish a stably transfected TOB1-overexpressing HBE cell line. A clonogenic assay was used to determine the radiosensitivity of the HBE cells with different TOB1 expression statuses. The cell cycle distribution was detected by flow cytometry. The ionizing radiation (IR)-induced γ-H2AX foci formation was detected by immunofluorescence assay. The related mechanism was explored by western blot analysis. TOB1 expression in the HBE cells was not induced by IR, neither dose-dependently nor timedependently. Compared to the parental or 'mock' transfected HBE cells, the radiosensitivity of HBE cells overexpressing TOB1 was significantly decreased (P<0.05). Exogenous TOB1 prevented HBE cells from apoptosis after IR, in contrast to the control cells (P<0.05), and significantly decreased the IR-induced γ-H2AX foci formation. After IR, the expression of DNA damage repair proteins such as XRCC1, MRE11, FEN1 and ATM was increased in the TOB1-overexpressing HBE cells when compared with the expression levels in the control cells. HBE/TOB1 cells presented a much higher phosphorylated ERK1/2 and phosphorylated p53 when compared with the levels in the control cell lines when receiving 6 Gy of X-rays. Notably, the increased expression of phosphorylated p53 in HBE/TOB1 cells after IR was sufficiently blocked by U0126, a specific inhibitor of MEK1/2. Different from its functions in several lung cancer cell lines, TOB1 demonstrated a radioprotective function in the immortalized normal human bronchial epithelial cell line HBE via the MAPK/ERK signaling pathway.

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Section: Discussionsupporting

confidence: 54%

“…A double-strand break (DSB) of DNA, the main biological target of IR, determines mutation or cell death after IR (17)(18)(19). The ability to repair DSBs determines the sensitivity of mammalian cells to IR (18,20).…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway

Chen

Sun

et al. 2013

Oncology Reports

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“…However, some pathways for DSB repair can mis-rejoin DNA ends from different break sites, thus creating chromosome aberrations. The influence of initial distance between DSB sites on the probability of mis-rejoining is under debate, as well as the possibility of mechanisms bringing DSB sites into closer vicinity during damage processing1. Estimates on break interaction distances based on biophysical modelling vary between 100 nm and several μm234.…”

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confidence: 99%

Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks

Girst

Hable

Drexler³

et al. 2013

Sci Rep

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The mobility of damaged chromatin regions in the nucleus may affect the probability of mis-repair. In this work, live-cell observation and distance tracking of GFP-tagged DNA damage response protein MDC1 was used to study the random-walk behaviour of chromatin domains containing radiation-induced DNA double-strand breaks (DSB). Our measurements indicate a subdiffusion-type random walk process with similar time dependence for isolated and clustered DSBs that were induced by 20 MeV proton or 43 MeV carbon ion micro-irradiation. As compared to normal diffusion, subdiffusion enhances the probability that both ends of a DSB meet, thus promoting high efficiency DNA repair. It also limits their probability of long-range movements and thus lowers the probability of mis-rejoining and chromosome aberrations.

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Radiation Biology of Radiation Protection

Hendry

2014

Comprehensive Biomedical Physics

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Double-strand break motions shift radiation risk notions?

Cited by 5 publications

References 20 publications

Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway

Overexpression of TOB1 confers radioprotection to bronchial epithelial cells through the MAPK/ERK pathway

Subdiffusion Supports Joining Of Correct Ends During Repair Of DNA Double-Strand Breaks

Radiation Biology of Radiation Protection

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