ArticleNucleic acids research2013
DNA damage signaling induced by the G-quadruplex ligand 12459 is modulated by PPM1D/WIP1 phosphatase.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Gain-of-function PPM1D mutations attenuate ischemic stroke.Cell death and differentiation · 2025Article
- Stabilization of G-Quadruplexes Modulates the Expression of DNA Damage and Unfolded Protein Response Genes in Canine Lymphoma/Leukemia Cells.International journal of molecular sciences · 2025Article
- The Molecular Characterization and Antioxidant Defense of a Novel Nrf2 from the Pacific AbaloneInternational journal of molecular sciences · 2024Article
- Genetic Predisposition to Myelodysplastic Syndromes: A Challenge for Adult Hematologists.International journal of molecular sciences · 2021Review
- Review
- G-Quadruplexes at Telomeres: Friend or Foe?Molecules (Basel, Switzerland) · 2020Review
- Targeting of PP2Cδ By a Small Molecule C23 Inhibits High Glucose-Induced Breast Cancer ProgressionAntioxidants & redox signaling · 2019Article
- Modulation of the ATM/autophagy pathway by a G-quadruplex ligand tips the balance between senescence and apoptosis in cancer cells.Nucleic acids research · 2019Article
- CD4+ memory T cells infected with latent HIV-1 are susceptible to drugs targeting telomeres.Cell cycle (Georgetown, Tex.) · 2018Article
- Telomerase and drug resistance in cancer.Cellular and molecular life sciences : CMLS · 2017Review
- Structure, Properties, and Biological Relevance of the DNA and RNA G-Quadruplexes: Overview 50 Years after Their Discovery.Biochemistry. Biokhimiia · 2016Article
- Phosphatase Wip1 controls antigen-independent B-cell development in a p53-dependent manner.Blood · 2015Article
- WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C.Oncotarget · 2015Article
- Targeting PPM1D by lentivirus-mediated RNA interference inhibits the tumorigenicity of bladder cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2014Article
- Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints.BMC genomics · 2014Article
- Nucleic acid detection using G-quadruplex amplification methodologies.Methods (San Diego, Calif.) · 2013Review
- G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells.Journal of the American Chemical Society · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The triazine derivative 12459 is a potent G-quadruplex ligand that triggers apoptosis or delayed growth arrest, telomere shortening and G-overhang degradation, as a function of its concentration and time exposure to the cells. We have investigated here the DNA damage response induced by 12459 in A549 cells. Submicromolar concentrations of 12459 triggers a delayed Chk1-ATR-mediated DNA damage response associated with a telomeric dysfunction and a G2/M arrest. Surprisingly, increasing concentrations of 12459 leading to cell apoptosis induced a mechanism that bypasses the DNA damage signaling and leads to the dephosphorylation of Chk1 and γ-H2AX. We identified the phosphatase Protein Phosphatase Magnesium dependent 1D/Wild-type P53-Induced Phosphatase (PPM1D/WIP1) as a factor responsible for this dephosphorylation. SiRNA-mediated depletion of PPM1D/WIP1 reactivates the DNA damage signaling by 12459. In addition, PPM1D/WIP1 is activated by reactive oxygen species (ROS) induced by 12459. ROS generated by 12459 are sufficient to trigger an early DNA damage in A549 cells when PPM1D/WIP1 is depleted. However, ROS inactivation by N-acetyl cysteine (NAC) treatment does not change the apoptotic response induced by 12459. Because PPM1D expression was recently reported to modulate the recruitment of DNA repair molecules, our data would suggest a cycle of futile protection against 12459, thus leading to a delayed mechanism of cell death.
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Registered trials
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.