ArticlePloS one2010
Dynamic dependence on ATR and ATM for double-strand break repair in human embryonic stem cells and neural descendants.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 116 citations in OpenAlex.
- Induced pluripotent stem cells from ataxia-telangiectasia recapitulate the cellular phenotype.Stem cells translational medicine · 2012Trial
- Stem cell models in ataxia-telangiectasia.Neural regeneration research · 2026Article
- Modeling the Acute Mucosal Toxicity of Fractionated Radiotherapy Combined with the ATM Inhibitor WSD0628.Molecular cancer therapeutics · 2025Article
- Cell-Type-Dependent Recruitment Dynamics of FUS Protein at Laser-Induced DNA Damage Sites.International journal of molecular sciences · 2024Article
- DNA Double Strand Break and Response Fluorescent Assays: Choices and Interpretation.International journal of molecular sciences · 2024Review
- Article
- LINCing Senescence and Nuclear Envelope Changes.Cells · 2022Review
- Regulation and coordination of the different DNA damage responses inFrontiers in cell and developmental biology · 2022Review
- The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age.Molecules (Basel, Switzerland) · 2021Review
- The Impact of Acquired Genetic Abnormalities on the Clinical Translation of Human Pluripotent Stem Cells.Cells · 2021Review
- Single cell heterogeneity in human pluripotent stem cells.BMB reports · 2021Article
- Phase I Study of Ceralasertib (AZD6738), a Novel DNA Damage Repair Agent, in Combination with Weekly Paclitaxel in Refractory Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Complex biology of constitutional ring chromosomes structure and (in)stability revealed by somatic cell reprogramming.Scientific reports · 2021Article
- Acquired genetic changes in human pluripotent stem cells: origins and consequences.Nature reviews. Molecular cell biology · 2020Review
- Chromosomal aberration arises during somatic reprogramming to pluripotent stem cells.Cell division · 2020Article
- Article
- Stage-Specific Effects of Ionizing Radiation during Early Development.International journal of molecular sciences · 2020Review
- Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer.Journal of hematology & oncology · 2020Review
- DNA repair fidelity in stem cell maintenance, health, and disease.Biochimica et biophysica acta. Molecular basis of disease · 2020Review
- Advances in Pluripotent Stem Cells: History, Mechanisms, Technologies, and Applications.Stem cell reviews and reports · 2020Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The DNA double-strand break (DSB) is the most toxic form of DNA damage. Studies aimed at characterizing DNA repair during development suggest that homologous recombination repair (HRR) is more critical in pluripotent cells compared to differentiated somatic cells in which nonhomologous end joining (NHEJ) is dominant. We have characterized the DNA damage response (DDR) and quality of DNA double-strand break (DSB) repair in human embryonic stem cells (hESCs), and in vitro-derived neural cells. Resolution of ionizing radiation-induced foci (IRIF) was used as a surrogate for DSB repair. The resolution of gamma-H2AX foci occurred at a slower rate in hESCs compared to neural progenitors (NPs) and astrocytes perhaps reflective of more complex DSB repair in hESCs. In addition, the resolution of RAD51 foci, indicative of active homologous recombination repair (HRR), showed that hESCs as well as NPs have high capacity for HRR, whereas astrocytes do not. Importantly, the ATM kinase was shown to be critical for foci formation in astrocytes, but not in hESCs, suggesting that the DDR is different in these cells. Blocking the ATM kinase in astrocytes not only prevented the formation but also completely disassembled preformed repair foci. The ability of hESCs to form IRIF was abrogated with caffeine and siRNAs targeted against ATR, implicating that hESCs rely on ATR, rather than ATM for regulating DSB repair. This relationship dynamically changed as cells differentiated. Interestingly, while the inhibition of the DNA-PKcs kinase (and presumably non-homologous endjoining [NHEJ]) in astrocytes slowed IRIF resolution it did not in hESCs, suggesting that repair in hESCs does not utilize DNA-PKcs. Altogether, our results show that hESCs have efficient DSB repair that is largely ATR-dependent HRR, whereas astrocytes critically depend on ATM for NHEJ, which, in part, is DNA-PKcs-independent.
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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.