ArticleProceedings of the National Academy of Sciences of the United States of America2013
APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 103 citations in OpenAlex.
- Two stress-responsive kinases suppress ferroptosis by activating antioxidant programs under mild oxidative stress.Signal transduction and targeted therapy · 2026Article
- Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond.International journal of molecular sciences · 2025Review
- Sexual dimorphism in zebrafish liver proteins and implications for hepatic regeneration and diseases.Scientific reports · 2025Article
- Castalin Induces ROS Production, Leading to DNA Damage and Increasing the Activity of CHK1 Inhibitor in Cancer Cell Lines.Antioxidants (Basel, Switzerland) · 2025Article
- Cisplatin-Induced APE2 Overexpression Disrupts MYH9 Function and Causes Hearing Loss.Cancer research communications · 2025Article
- FNDC5/irisin mitigates the cardiotoxic impacts of cancer chemotherapeutics by modulating ROS-dependent and -independent mechanisms.Redox biology · 2025Article
- DNA damage response regulator ATR licenses PINK1-mediated mitophagy.Nucleic acids research · 2025Article
- Review
- Distinct regulation of ATM signaling by DNA single-strand breaks and APE1.Nature communications · 2024Article
- Myeloid-derived suppressor cell mitochondrial fitness governs chemotherapeutic efficacy in hematologic malignancies.Nature communications · 2024Article
- Key molecular DNA damage responses of human cells to radiation.Frontiers in cell and developmental biology · 2024Review
- Hyperosmotic stress induces 2-cell-like cells through ROS and ATR signaling.EMBO reports · 2023Article
- Inner Amino Acid Contacts Are Key Factors of Multistage Structural Rearrangements of DNA and Affect Substrate Specificity of Apurinic/Apyrimidinic Endonuclease APE1.International journal of molecular sciences · 2023Article
- Article
- The APE2 nuclease is essential for DNA double-strand break repair by microhomology-mediated end joining.Molecular cell · 2023Article
- Claspin-Dependent and -Independent Chk1 Activation by a Panel of Biological Stresses.Biomolecules · 2023Article
- Kinetic Features of 3'-5'-Exonuclease Activity of Apurinic/Apyrimidinic Endonuclease Apn2 fromInternational journal of molecular sciences · 2022Article
- APE1 assembles biomolecular condensates to promote the ATR-Chk1 DNA damage response in nucleolus.Nucleic acids research · 2022Article
- The APE2 Exonuclease Is a Client of the Hsp70-Hsp90 Axis in Yeast and Mammalian Cells.Biomolecules · 2022Article
- Non-enzymatic function of WRN RECQL helicase regulates removal of topoisomerase-I-DNA covalent complexes and triggers NF-κB signaling in cancer.Aging cell · 2022Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The base excision repair pathway is largely responsible for the repair of oxidative stress-induced DNA damage. However, it remains unclear how the DNA damage checkpoint is activated by oxidative stress at the molecular level. Here, we provide evidence showing that hydrogen peroxide (H2O2) triggers checkpoint kinase 1 (Chk1) phosphorylation in an ATR [ataxia-telangiectasia mutated (ATM) and Rad3-related]-dependent but ATM-independent manner in Xenopus egg extracts. A base excision repair protein, Apurinic/apyrimidinic (AP) endonuclease 2 (APE2, APN2, or APEX2), is required for the generation of replication protein A (RPA)-bound single-stranded DNA, the recruitment of a checkpoint protein complex [ATR, ATR-interacting protein (ATRIP), and Rad9] to damage sites, and H2O2-induced Chk1 phosphorylation. A conserved proliferating cell nuclear antigen interaction protein box of APE2 is important for the recruitment of APE2 to H2O2-damaged chromatin. APE2 3'-phosphodiesterase and 3'-5' exonuclease activity is essential for single-stranded DNA generation in the 3'-5' direction from single-stranded breaks, referred to as single-stranded break end resection. In addition, APE2 associates with Chk1, and a serine residue (S86) in the Chk1-binding motif of APE2 is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 in ATR-Chk1 signaling. Our data indicate that APE2 plays a vital and previously unexpected role in ATR-Chk1 checkpoint signaling in response to oxidative stress. Thus, our findings shed light on a distinct mechanism of how an ATR-Chk1-dependent DNA damage checkpoint is mediated by APE2 in the oxidative stress response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.