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...

Full description

Bibliographic Details
Main Authors: Ako Matsui, Kazunari Hashiguchi, Masao Suzuki, Qiu-Mei Zhang-Akiyama
Format: Article
Language:English
Published: BMC 2020-11-01
Series:Genes and Environment
Subjects:
Online Access:http://link.springer.com/article/10.1186/s41021-020-00168-w
_version_ 1819169603513745408
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
record_format Article
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
work_keys_str_mv AT akomatsui oxidationresistance1functionsinthemaintenanceofcellularsurvivalandgenomestabilityinresponsetooxidativestressindependentdnadamage
AT kazunarihashiguchi oxidationresistance1functionsinthemaintenanceofcellularsurvivalandgenomestabilityinresponsetooxidativestressindependentdnadamage
AT masaosuzuki oxidationresistance1functionsinthemaintenanceofcellularsurvivalandgenomestabilityinresponsetooxidativestressindependentdnadamage
AT qiumeizhangakiyama oxidationresistance1functionsinthemaintenanceofcellularsurvivalandgenomestabilityinresponsetooxidativestressindependentdnadamage