ArticleScience advances2023
ATM-SPARK: A GFP phase separation-based activity reporter of ATM.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Noninvasive methods to monitor dynamic single-cell events.Trends in cell biology · 2026Review
- Article
- Review
- Visualizing PINK1 Activity Dynamics in Single Cells with a Phase Separation-Based Kinase Activity Reporter.ACS sensors · 2026Article
- Biomolecular Condensates in Disease: Decoding the Material State and Engineering Precision Modulators.International journal of molecular sciences · 2026Review
- Condensatopathies as a mechanistic framework for disease and integrated theranostic intervention.Theranostics · 2026Review
- Visualizing PINK1 Activity Dynamics in Single Cells with a Phase Separation-Based Kinase Activity Reporter.bioRxiv : the preprint server for biology · 2025Article
- UCHL3: a crucial deubiquitinase in DNA damage repair and tumor progression.Cancer cell international · 2025Review
- Development of a Dual Reporter System to Simultaneously Visualize CaACS sensors · 2024Article
- Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TORSEL, a 4EBP1-based mTORC1 live-cell sensor, reveals nutrient-sensing targeting by histone deacetylase inhibitors.Cell & bioscience · 2024Article
- Polarized focal adhesion kinase activity within a focal adhesion during cell migration.Nature chemical biology · 2023Article
- Article
- Phase separation-based visualization of protein-protein interactions and kinase activities in plants.The Plant cell · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The kinase ataxia telangiectasia mutated (ATM) plays a key role in the DNA damage response (DDR). It is thus essential to visualize spatiotemporal dynamics of ATM activity during DDR. Here, we designed a robust ATM activity reporter based on phosphorylation-inducible green fluorescent protein phase separation, dubbed ATM-SPARK (separation of phases-based activity reporter of kinase). Upon ATM activation, it undergoes phase separation via multivalent interactions, forming intensely bright droplets. The reporter visualizes spatiotemporal dynamics of endogenous ATM activity in living cells, and its signal is proportional to the amount of DNA damage. ATM-SPARK also enables high-throughput screening of biological and small-molecule regulators. We identified the protein phosphatase 4 that blocks ATM activity. We also identified BGT226 as a potent ATM inhibitor with a median inhibitory concentration of ~3.8 nanomolars. Furthermore, BGT226 sensitizes cancer cells to the radiomimetic drug neocarzinostatin, suggesting that BGT226 might be combined with radiotherapeutic treatment. ATM-SPARK achieves large dynamic range, bright fluorescence, and simple signal pattern.
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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.