Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage
Abstract Background DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is...
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BMC
2020-11-01
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Series: | Genes and Environment |
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Online Access: | http://link.springer.com/article/10.1186/s41021-020-00168-w |
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author | Ako Matsui Kazunari Hashiguchi Masao Suzuki Qiu-Mei Zhang-Akiyama |
author_facet | Ako Matsui Kazunari Hashiguchi Masao Suzuki Qiu-Mei Zhang-Akiyama |
author_sort | Ako Matsui |
collection | DOAJ |
description | Abstract Background DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is a protein that defends cells against oxidative stress. We previously reported that OXR1 protein functions in the regulation of G2-phase cell cycle arrest in cells irradiated with gamma-rays, suggesting that OXR1 directly responds to DNA damage. Purpose To clarify the functions of OXR1 against ROS-independent DNA damage, HeLa and OXR1-depleted HeLa cells were treated with heavy-ion beams and the ROS-independent DNA-damaging agent methyl methanesulfonate (MMS). Results First, OXR1-depleted cells exhibited higher sensitivity to MMS and heavy-ion beams than control cells. Next, OXR1 depletion increased micronucleus formation and shortened the duration of G2-phase arrest after treatment with MMS or heavy-ion beams. These results suggest that OXR1 functions in the maintenance of cell survival and genome stability in response to DNA damage. Furthermore, the OXR1 protein level was increased by MMS and heavy-ion beams in HeLa cells. Conclusions Together with our previous study, the present study suggests that OXR1 plays an important role in the response to DNA damage, not only when DNA damage is generated by ROS. |
first_indexed | 2024-12-22T19:22:08Z |
format | Article |
id | doaj.art-23175cc4eb0040bdb750a587c0612d25 |
institution | Directory Open Access Journal |
issn | 1880-7062 |
language | English |
last_indexed | 2024-12-22T19:22:08Z |
publishDate | 2020-11-01 |
publisher | BMC |
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series | Genes and Environment |
spelling | doaj.art-23175cc4eb0040bdb750a587c0612d252022-12-21T18:15:21ZengBMCGenes and Environment1880-70622020-11-014211610.1186/s41021-020-00168-wOxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damageAko Matsui0Kazunari Hashiguchi1Masao Suzuki2Qiu-Mei Zhang-Akiyama3Laboratory of Stress Response Biology, Department of Zoology, Division of Biological Sciences, Graduate School of Science, Kyoto UniversityLaboratory of Stress Response Biology, Department of Zoology, Division of Biological Sciences, Graduate School of Science, Kyoto UniversityDepartment of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and TechnologyLaboratory of Stress Response Biology, Department of Zoology, Division of Biological Sciences, Graduate School of Science, Kyoto UniversityAbstract Background DNA damage is generated by various intrinsic and extrinsic sources such as reactive oxygen species (ROS) and environmental mutagens, and causes genomic alterations. DNA damage response (DDR) is activated to induce cell cycle arrest and DNA repair. Oxidation resistance 1 (OXR1) is a protein that defends cells against oxidative stress. We previously reported that OXR1 protein functions in the regulation of G2-phase cell cycle arrest in cells irradiated with gamma-rays, suggesting that OXR1 directly responds to DNA damage. Purpose To clarify the functions of OXR1 against ROS-independent DNA damage, HeLa and OXR1-depleted HeLa cells were treated with heavy-ion beams and the ROS-independent DNA-damaging agent methyl methanesulfonate (MMS). Results First, OXR1-depleted cells exhibited higher sensitivity to MMS and heavy-ion beams than control cells. Next, OXR1 depletion increased micronucleus formation and shortened the duration of G2-phase arrest after treatment with MMS or heavy-ion beams. These results suggest that OXR1 functions in the maintenance of cell survival and genome stability in response to DNA damage. Furthermore, the OXR1 protein level was increased by MMS and heavy-ion beams in HeLa cells. Conclusions Together with our previous study, the present study suggests that OXR1 plays an important role in the response to DNA damage, not only when DNA damage is generated by ROS.http://link.springer.com/article/10.1186/s41021-020-00168-wOXR1DNA damage responseCell cycle checkpointCellular survivalProtein expression |
spellingShingle | Ako Matsui Kazunari Hashiguchi Masao Suzuki Qiu-Mei Zhang-Akiyama Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage Genes and Environment OXR1 DNA damage response Cell cycle checkpoint Cellular survival Protein expression |
title | Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage |
title_full | Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage |
title_fullStr | Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage |
title_full_unstemmed | Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage |
title_short | Oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress-independent DNA damage |
title_sort | oxidation resistance 1 functions in the maintenance of cellular survival and genome stability in response to oxidative stress independent dna damage |
topic | OXR1 DNA damage response Cell cycle checkpoint Cellular survival Protein expression |
url | http://link.springer.com/article/10.1186/s41021-020-00168-w |
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