ArticleCancers2019
Uniform Widespread Nuclear Phosphorylation of Histone H2AX Is an Indicator of Lethal DNA Replication Stress.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- Oligodendroglial somatic SNCA copy number gains are associated with inclusions and disease onset in multiple system atrophy.Acta neuropathologica · 2026Article
- Developmental Control of DNA Damage Responses in α- and β-Cells Shapes the Selective β-Cell Susceptibility in Diabetes.Diabetes · 2026Article
- MCM3 Safeguards Neural Progenitor Maintenance and Cortical Development Against Replication-Associated Stress.Molecular neurobiology · 2026Article
- Replication origin firing capacity indicates ATR inhibitor sensitivity.Nature communications · 2026Article
- Tilting the balance of life and death: navigating DNA replication stress in cancer therapy.Experimental & molecular medicine · 2026Review
- ATR enforcement of the S/G2 checkpoint prevents premature S phase shutdown and genome instability.bioRxiv : the preprint server for biology · 2026Article
- ATR and PKMYT1 Inhibition Resensitizes a Subset of TNBC Patient-Derived Models to Carboplatin, Inducing Mitotic Catastrophe.Cancer research communications · 2026Article
- Precise metabolomics identifies glycolysis-related pyruvate kinase M activity as regulator of the S-phase-specific radiation response in triple-negative breast cancer cells.Cell communication and signaling : CCS · 2026Article
- DNA damage response defects induced by the formation of TDP-43 and mutant FUS cytoplasmic inclusions and their pharmacological rescue.Cell death and differentiation · 2025Article
- The DNA-PKcs/JNK/p53 pathway underlies changes in cell fate decision toward death during DNA replication catastrophe.Nucleic acids research · 2025Article
- Exogenous LEA proteins expression enhances cold tolerance in mammalian cells by reducing oxidative stress.Scientific reports · 2025Article
- Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice.Journal of biomedical science · 2025Article
- A novel DNA damage detection method based on a distinct DNA damage response system.Microbial biotechnology · 2024Article
- The timing of pronuclear transfer critically affects the developmental competence and quality of embryos.Molecular human reproduction · 2024Article
- Synthesis and new DNA targeting activity of 6- and 7-tert-butylfascaplysins.Scientific reports · 2024Article
- DNA damage response in a 2D-culture model by diffusing alpha-emitters radiation therapy (Alpha-DaRT).Scientific reports · 2024Article
- FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe.DNA repair · 2024Article
- Genome homeostasis defects drive enlarged cells into senescence.Molecular cell · 2023Article
- Replisome dysfunction upon inducible TIMELESS degradation synergizes with ATR inhibition to trigger replication catastrophe.Nucleic acids research · 2023Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Phosphorylated histone H2AX (γ-H2AX), a central player in the DNA damage response (DDR), serves as a biomarker of DNA double-strand break repair. Although DNA damage is generally visualized by the formation of γ-H2AX foci in injured nuclei, it is unclear whether the widespread uniform nuclear γ-H2AX (called pan-nuclear) pattern occurring upon intense replication stress (RS) is linked to DDR. Using a novel monoclonal antibody that binds exclusively to the phosphorylated C-terminus of H2AX, we demonstrate that H2AX phosphorylation is systematically pan-nuclear in cancer cells stressed with RS-inducing drugs just before they die. The pan-nuclear γ-H2AX pattern is abolished by inhibition of the DNA-PK kinase. Cell death induction of cancer cells treated with increasing combinations of replication and kinase (ATR and Chk1) inhibitory drugs was proportional to the appearance of pan-nuclear γ-H2AX pattern. Delivery of labeled anti-γ-H2AX Fabs in stressed cells demonstrated at a single cell level that pan-nuclear γ-H2AX formation precedes irreversible cell death. Moreover, we show that H2AX is not required for RS-induced cell death in HeLa cells. Thus, the nuclear-wide formation of γ-H2AX is an incident of RS-induced cell death and, thus, the pan nuclear H2AX pattern should be regarded as an indicator of lethal RS-inducing drug efficacy.
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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.