ArticleCancer discovery2024
GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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.
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Who cites it
17 citing papers in PubMed, 59 citations in OpenAlex.
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- Dynamic Monitoring of Content Variation of Guanosine Triphosphate in Single Cells under External Stimulus with Functionalized Fluorescent/Photothermal NbChemical & biomedical imaging · 2026Article
- The Rac1-USP11 feedback amplification loop: a radiation-activated engine driving radioresistance in hepatocellular carcinoma.British journal of cancer · 2026Article
- Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment.Neuro-oncology · 2026Article
- Digital twins for in vivo metabolic flux estimations in patients with brain cancer.Cell metabolism · 2026Article
- The extracellular matrix drives guanylate production and protects pancreatic cancer cells from oxaliplatin-induced DNA damage.Science advances · 2025Article
- IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.Cancer science · 2025Review
- Adaptive nuclear GTP synthesis promotes glioblastoma treatment resistance and is a targetable vulnerability in patients.medRxiv : the preprint server for health sciences · 2025Article
- Article
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- Metabolic Rewiring in the Face of Genomic Assault: Integrating DNA Damage Response and Cellular Metabolism.Biomolecules · 2025Review
- Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.Scientific reports · 2025Article
- 2-Deoxy-D-Glucose and ES-936 sensitize cancer- but not normal cells to both low- and high LET irradiation.Frontiers in oncology · 2025Article
- Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration.Journal of molecular neuroscience : MN · 2024Review
- High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.Cell death and differentiation · 2024Article
- Purine salvage promotes treatment resistance in H3K27M-mutant diffuse midline glioma.Cancer & metabolism · 2024Article
- Identification of an inflammatory response-related gene prognostic signature and immune microenvironment for cervical cancer.Frontiers in molecular biosciences · 2024Article
Corrections and comments
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Authors and funding
40 authors at 8 institutions in 3 countries.
Funding
Abstract
How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment. SIGNIFICANCE: A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5.
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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.