ArticleNucleic acids research2021
Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 223 citations in OpenAlex.
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- Microglial Alkbh5 Deficiency Alleviates Chronic Restraint Stress-Induced Depression-like Behaviors in Mice.Neuroscience bulletin · 2026Article
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- AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction.Addiction biology · 2026Review
- RNA modification-mediated multidimensional crosstalk: a novel perspective on gene expression regulation.Genome biology · 2026Review
- m6A RNA methylation in neural plasticity, brain aging, and neurodegenerative vulnerability.Molecular brain · 2026Review
- The N6-Methyladenosine RNA Demethylase AlkB Homolog 5 (ALKBH5) in Metabolic Diseases: Molecular Mechanisms and Pharmacological Implications-A Review.Biomolecules · 2026Review
- Targeting mDiscover oncology · 2026Review
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- Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Dynamic modulation of N6-methyladenosine by ionizing radiation in human cells.Biochemistry and biophysics reports · 2026Article
- Redox-Guided Epigenetic Signaling in Cancer: miRNA-DNMT Feedback Loops as Epigenetic Memory Modulates.Antioxidants (Basel, Switzerland) · 2026Review
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Elevated m 6 A RNA Modifications Associate with Immune Dysregulation and Cancer in People with HIV-1.Research square · 2026Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Faithful genome integrity maintenance plays an essential role in cell survival. Here, we identify the RNA demethylase ALKBH5 as a key regulator that protects cells from DNA damage and apoptosis during reactive oxygen species (ROS)-induced stress. We find that ROS significantly induces global mRNA N6-methyladenosine (m6A) levels by modulating ALKBH5 post-translational modifications (PTMs), leading to the rapid and efficient induction of thousands of genes involved in a variety of biological processes including DNA damage repair. Mechanistically, ROS promotes ALKBH5 SUMOylation through activating ERK/JNK signaling, leading to inhibition of ALKBH5 m6A demethylase activity by blocking substrate accessibility. Moreover, ERK/JNK/ALKBH5-PTMs/m6A axis is activated by ROS in hematopoietic stem/progenitor cells (HSPCs) in vivo in mice, suggesting a physiological role of this molecular pathway in the maintenance of genome stability in HSPCs. Together, our study uncovers a molecular mechanism involving ALKBH5 PTMs and increased mRNA m6A levels that protect genomic integrity of cells in response to ROS.
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