ArticleProceedings of the National Academy of Sciences of the United States of America2012
Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.
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123 citing papers in PubMed.
- Base-excision repair increases DNA double-strand break clustering within heavy-ion tracks and modulates repair at δ-electron-induced breaks.Scientific reports · 2026Article
- Genome scale CRISPR screens identify actin capping proteins as key modulators of therapeutic responses to radiation and immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Misleading Model: Why the 5% Cancer Risk from Computed Tomography Scans Is Overstated.American journal of respiratory and critical care medicine · 2025Article
- Effect of gamma-ray exposure on the genome-editing efficiency of improved genome-editing via oviductal nucleic acids delivery (i-GONAD).Experimental animals · 2025Article
- Single nucleosome imaging reveals principles of transient multiscale chromatin reorganization triggered by histone ADP-ribosylation at DNA lesions.Nature communications · 2025Article
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- γ-tubulin mediates DNA double-strand break repair.Journal of cell science · 2025Article
- Targeted radioligand therapy: physics and biology, internal dosimetry and other practical aspects duringTheranostics · 2025Review
- Population Studies and Molecular Mechanisms of Human Radioadaptive Capabilities: Is It Time to Rethink Radiation Safety Standards?International journal of molecular sciences · 2024Review
- TIP60 enhances cisplatin resistance via regulating ΔNp63α acetylation in SCC.Cell death & disease · 2024Article
- Genome-wide profiling of DNA repair proteins in single cells.Nature communications · 2024Article
- Rectal Epithelial Stem Cell Kinetics in Acute Radiation Proctitis.International journal of molecular sciences · 2024Article
- Early and Late Effects of Low-Dose X-ray Exposure in Human Fibroblasts: DNA Repair Foci, Proliferation, Autophagy, and Senescence.International journal of molecular sciences · 2024Article
- A 3D In Vitro Cortical Tissue Model Based on Dense Collagen to Study the Effects of Gamma Radiation on Neuronal Function.Advanced healthcare materials · 2024Article
- DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.Pharmaceutics · 2023Review
- A human lung alveolus-on-a-chip model of acute radiation-induced lung injury.Nature communications · 2023Article
- Specificity of cancer-related chromosomal translocations is linked to proximity after the DNA double-strand break and subsequent selection.NAR cancer · 2023Article
- Non-linear dose response of DNA double strand breaks in response to chronic low dose radiation in individuals from high level natural radiation areas of Kerala coast.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2023Article
- Working with Convex Responses: Antifragility from Finance to Oncology.Entropy (Basel, Switzerland) · 2023Article
- Multiscale reorganization of the genome following DNA damage facilitates chromosome translocations via nuclear actin polymerization.Nature structural & molecular biology · 2023Article
63 more citing papers are in PubMed but not listed here.
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12 authors.
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Abstract
The concept of DNA "repair centers" and the meaning of radiation-induced foci (RIF) in human cells have remained controversial. RIFs are characterized by the local recruitment of DNA damage sensing proteins such as p53 binding protein (53BP1). Here, we provide strong evidence for the existence of repair centers. We used live imaging and mathematical fitting of RIF kinetics to show that RIF induction rate increases with increasing radiation dose, whereas the rate at which RIFs disappear decreases. We show that multiple DNA double-strand breaks (DSBs) 1 to 2 μm apart can rapidly cluster into repair centers. Correcting mathematically for the dose dependence of induction/resolution rates, we observe an absolute RIF yield that is surprisingly much smaller at higher doses: 15 RIF/Gy after 2 Gy exposure compared to approximately 64 RIF/Gy after 0.1 Gy. Cumulative RIF counts from time lapse of 53BP1-GFP in human breast cells confirmed these results. The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, our discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation.
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