ArticleStem cells (Dayton, Ohio)2009
Ionizing radiation induces ataxia telangiectasia mutated-dependent checkpoint signaling and G(2) but not G(1) cell cycle arrest in pluripotent human embryonic stem cells.
Article in Stem cells (Dayton, Ohio), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 142 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
- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
- ATM knock out alters calcium signalling and augments contraction in skeletal muscle cells differentiated from human urine-derived stem cells.Cell death discovery · 2025Article
- DNA-damage orchestrates self-renewal and differentiation via reciprocal p53 family and Hippo/Wnt/TGF-β pathway activation in embryonic stem cells.Cellular and molecular life sciences : CMLS · 2025Article
- Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration.Life (Basel, Switzerland) · 2021Review
- Telomere erosion in human pluripotent stem cells leads to ATR-mediated mitotic catastrophe.The Journal of cell biology · 2021Article
- Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells.PloS one · 2021Article
- Acquired genetic changes in human pluripotent stem cells: origins and consequences.Nature reviews. Molecular cell biology · 2020Review
- Article
- Stage-Specific Effects of Ionizing Radiation during Early Development.International journal of molecular sciences · 2020Review
- A long noncoding RNA sensitizes genotoxic treatment by attenuating ATM activation and homologous recombination repair in cancers.PLoS biology · 2020Article
- Inactivation of PLK4-STIL Module Prevents Self-Renewal and Triggers p53-Dependent Differentiation in Human Pluripotent Stem Cells.Stem cell reports · 2018Article
- Low-dose irradiation of mouse embryos increases Smad-p21 pathway activity and preserves pluripotency.Journal of assisted reproduction and genetics · 2018Article
- Counteracting survival functions of EBNA3C in Epstein-Barr virus (EBV)-driven lymphoproliferative diseases by combination of SAHA and bortezomib.Oncotarget · 2018Article
- Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.Cell death discovery · 2018Review
- Optimization of culture conditions for the derivation and propagation of baboon (Papio anubis) induced pluripotent stem cells.PloS one · 2018Article
- Differentiation of Human Induced Pluripotent or Embryonic Stem Cells Decreases the DNA Damage Repair by Homologous Recombination.Stem cell reports · 2017Article
- Irradiation strongly reduces tumorigenesis of human induced pluripotent stem cells.Journal of radiation research · 2017Article
- Early Passage Mesenchymal Stem Cells Display Decreased Radiosensitivity and Increased DNA Repair Activity.Stem cells translational medicine · 2017Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Human embryonic stem (ES) cells are highly sensitive to environmental insults including DNA damaging agents, responding with high levels of apoptosis. To understand the response of human ES cells to DNA damage, we investigated the function of the ataxia telangiectasia mutated (ATM) DNA damage signaling pathway in response to gamma-irradiation. Here, we demonstrate for the first time in human ES cells that ATM kinase is phosphorylated and properly localized to the sites of DNA double-strand breaks within 15 minutes of irradiation. Activation of ATM kinase resulted in phosphorylation of its downstream targets: Chk2, p53, and Nbs1. In contrast to murine ES cells, Chk2 and p53 were localized to the nucleus of irradiated human ES cells. We further show that irradiation resulted in a temporary arrest of the cell cycle at the G(2), but not G(1), phase. Human ES cells resumed cycling approximately 16 hours after irradiation, but had a fourfold higher incidence of aberrant mitotic figures compared to nonirradiated cells. Finally, we demonstrate an essential role of ATM in establishing G(2) arrest since inhibition with the ATM-specific inhibitor KU55933 resulted in abolishment of G(2) arrest, evidenced by an increase in the number of cycling cells 2 hours after irradiation. In summary, these results indicate that human ES cells activate the DNA damage checkpoint, resulting in an ATM-dependent G(2) arrest. However, these cells re-enter the cell cycle with prominent mitotic spindle defects.
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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.