Oxidation resistance 1 prevents genome instability through maintenance of G2/M arrest in gamma-ray-irradiated cells
| Autor: | Junya Kobayashi, Akira Yasui, Kazunari Hashiguchi, Yukihiro Yoshikawa, Masahiro Miyaji, Shin Ichiro Kanno, Ako Matsui, Qiu-Mei Zhang-Akiyama |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Genome instability
Cell cycle checkpoint Health Toxicology and Mutagenesis Mitosis medicine.disease_cause Models Biological Genomic Instability Mitochondrial Proteins HeLa 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cyclin D1 Superoxides Regular Paper medicine Humans Radiology Nuclear Medicine and imaging 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Radiation biology Superoxide OXR1 Hydrogen Peroxide Cell cycle biology.organism_classification Cell biology G2 Phase Cell Cycle Checkpoints Oxidative Stress chemistry cell cycle arrest Gamma Rays 030220 oncology & carcinogenesis Micronucleus Germline genome stability Oxidative stress HeLa Cells |
| Zdroj: | Journal of Radiation Research |
| ISSN: | 1349-9157 0449-3060 |
| Popis: | Human oxidation resistance 1 (OXR1) was identified as a protein that decreases genomic mutations in Escherichia coli caused by oxidative DNA damage. However, the mechanism by which OXR1 defends against genome instability has not been elucidated. To clarify how OXR1 maintains genome stability, the effects of OXR1-depletion on genome stability were investigated in OXR1-depleted HeLa cells using gamma-rays (γ-rays). The OXR1-depleted cells had higher levels of superoxide and micronucleus (MN) formation than control cells after irradiation. OXR1-overexpression alleviated the increases in reactive oxygen species (ROS) level and MN formation after irradiation. The increased MN formation in irradiated OXR1-depleted cells was partially attenuated by the ROS inhibitor N-acetyl-L-cysteine, suggesting that OXR1-depeletion increases ROS-dependent genome instability. We also found that OXR1-depletion shortened the duration of γ-ray-induced G2/M arrest. In the presence of the cell cycle checkpoint inhibitor caffeine, the level of MN formed after irradiation was similar between control and OXR1-depleted cells, demonstrating that OXR1-depletion accelerates MN formation through abrogation of G2/M arrest. In OXR1-depleted cells, the level of cyclin D1 protein expression was increased. Here we report that OXR1 prevents genome instability by cell cycle regulation as well as oxidative stress defense. |
| Databáze: | OpenAIRE |
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