Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

Abstract 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...

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Autores principales:	Munetoshi Maeda, Masanori Tomita, Mika Maeda, Hideki Matsumoto, Noriko Usami, Kyo Kume, Katsumi Kobayashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e08a50dc6f584bd08fee092c4dae0a7e
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spelling	oai:doaj.org-article:e08a50dc6f584bd08fee092c4dae0a7e2021-12-02T18:33:57ZExposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses10.1038/s41598-021-92213-z2045-2322https://doaj.org/article/e08a50dc6f584bd08fee092c4dae0a7e2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92213-zhttps://doaj.org/toc/2045-2322Abstract 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.Munetoshi MaedaMasanori TomitaMika MaedaHideki MatsumotoNoriko UsamiKyo KumeKatsumi KobayashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Munetoshi Maeda Masanori Tomita Mika Maeda Hideki Matsumoto Noriko Usami Kyo Kume Katsumi Kobayashi Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
description	Abstract 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.
format	article
author	Munetoshi Maeda Masanori Tomita Mika Maeda Hideki Matsumoto Noriko Usami Kyo Kume Katsumi Kobayashi
author_facet	Munetoshi Maeda Masanori Tomita Mika Maeda Hideki Matsumoto Noriko Usami Kyo Kume Katsumi Kobayashi
author_sort	Munetoshi Maeda
title	Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
title_short	Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
title_full	Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
title_fullStr	Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
title_full_unstemmed	Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses
title_sort	exposure of the cytoplasm to low-dose x-rays modifies ataxia telangiectasia mutated-mediated dna damage responses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e08a50dc6f584bd08fee092c4dae0a7e
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Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

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