Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
| Autor: | Noriko Usami, Munetoshi Maeda, Mika Maeda, Hideki Matsumoto, Masanori Tomita, K. Kobayashi, Kyo Kume |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 Cell death Programmed cell death Cytoplasm Cell cycle checkpoint DNA Repair DNA damage Science Ataxia Telangiectasia Mutated Proteins Article Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetulus medicine Animals Humans DNA Breaks Double-Stranded Phosphorylated Histone H2AX Multidisciplinary Kinase Chemistry DNA damage and repair Cell Cycle Checkpoints DNA Molecular biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Medicine Nucleus DNA Damage Signal Transduction Cell signalling |
| Zdroj: | Scientific Reports Scientific Reports, Vol 11, Iss 1, Pp 1-13 (2021) |
| ISSN: | 2045-2322 |
| Popis: | We recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses. |
| Databáze: | OpenAIRE |
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