ArticleThe EMBO journal2021
Phosphoproteomics reveals novel modes of function and inter-relationships among PIKKs in response to genotoxic stress.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- DNA-PK-mediated CRTC2 phosphorylation promotes NHEJ and suppresses antitumor immunity via relocation to repair complexes.Nature communications · 2026Article
- ZC3H4 safeguards genome integrity by preventing transcription-replication conflicts at noncoding RNA loci.Science advances · 2025Article
- Article
- Profile of Yosef Shiloh.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The cGAS-STING, p38 MAPK, and p53 pathways link genome instability to accelerated cellular senescence in ATM-deficient murine lung fibroblasts.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- OTUD5 promotes end-joining of deprotected telomeres by promoting ATM-dependent phosphorylation of KAP1Nature communications · 2024Article
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- Poly(ADP-Ribose) Polymerase Inhibitor Development: Promising Strategies to Move Beyond Approved Indications.JCO precision oncology · 2024Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN.NAR cancer · 2024Article
- A-T neurodegeneration and DNA damage-induced transcriptional stress.DNA repair · 2024Review
- IN-DEPTH MAPPING OF DNA-PKcs SIGNALING UNCOVERS CONSERVED FEATURES OF ITS KINASE SPECIFICITY.bioRxiv : the preprint server for biology · 2024Article
- ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Cyclers' kinases in cell division: from molecules to cancer therapy.Cell death and differentiation · 2023Review
- Ataxia-telangiectasia mutated plays an important role in cerebellar integrity and functionality.Neural regeneration research · 2023Review
- Recruitment of RBM6 to DNA Double-Strand Breaks Fosters Homologous Recombination Repair.Molecular and cellular biology · 2023Article
- Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The DNA damage response (DDR) is a complex signaling network that relies on cascades of protein phosphorylation, which are initiated by three protein kinases of the family of PI3-kinase-related protein kinases (PIKKs): ATM, ATR, and DNA-PK. ATM is missing or inactivated in the genome instability syndrome, ataxia-telangiectasia (A-T). The relative shares of these PIKKs in the response to genotoxic stress and the functional relationships among them are central questions in the genome stability field. We conducted a comprehensive phosphoproteomic analysis in human wild-type and A-T cells treated with the double-strand break-inducing chemical, neocarzinostatin, and validated the results with the targeted proteomic technique, selected reaction monitoring. We also matched our results with 34 published screens for DDR factors, creating a valuable resource for identifying strong candidates for novel DDR players. We uncovered fine-tuned dynamics between the PIKKs following genotoxic stress, such as DNA-PK-dependent attenuation of ATM. In A-T cells, partial compensation for ATM absence was provided by ATR and DNA-PK, with distinct roles and kinetics. The results highlight intricate relationships between these PIKKs in the DDR.
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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.