ArticleThe Journal of biological chemistry2016
ATR Kinase Inhibition Protects Non-cycling Cells from the Lethal Effects of DNA Damage and Transcription Stress.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Article
- Targeting ATR and PI3Kα Pathways Promotes Ferroptosis inCancers · 2026Article
- Differential effects of mercury compounds on mutagenicity, genotoxicity and repair of UV-DNA damage.Toxicology · 2025Article
- Solar ultraviolet-induced DNA damage response: Melanocytes story in transformation to environmental melanomagenesis.Environmental and molecular mutagenesis · 2020Review
- The 6-4 photoproduct is the trigger of UV-induced replication blockage and ATR activation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Deciphering UV-induced DNA Damage Responses to Prevent and Treat Skin Cancer.Photochemistry and photobiology · 2020Review
- ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation.Photochemistry and photobiology · 2020Article
- ATR kinase inhibition sensitizes quiescent human cells to the lethal effects of cisplatin but increases mutagenesis.Mutation research · 2019Article
- Nucleotide excision repair capacity increases during differentiation of human embryonic carcinoma cells into neurons and muscle cells.The Journal of biological chemistry · 2019Article
- Regulation of ATR activity via the RNA polymerase II associated factors CDC73 and PNUTS-PP1.Nucleic acids research · 2019Article
- Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin.The Journal of investigative dermatology · 2019Article
- VE-822 mediated inhibition of ATR signaling sensitizes chondrosarcoma to cisplatin via reversion of the DNA damage response.OncoTargets and therapy · 2019Article
- Imaging cellular responses to antigen tagged DNA damage.DNA repair · 2018Review
- Roles of UVA radiation and DNA damage responses in melanoma pathogenesis.Environmental and molecular mutagenesis · 2018Review
- A novel role for ATR/Rad3 in G1 phase.Scientific reports · 2018Article
- A New Way to Treat Brain Tumors: Targeting Proteins Coded by Microcephaly Genes?: Brain tumors and microcephaly arise from opposing derangements regulating progenitor growth. Drivers of microcephaly could be attractive brain tumor targets.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018Review
- Reevaluation of ATR signaling in primary resting chronic lymphocytic leukemia cells: evidence for pro-survival or pro-apoptotic function.Oncotarget · 2017Article
- DNA damage-induced ATM- and Rad-3-related (ATR) kinase activation in non-replicating cells is regulated by the XPB subunit of transcription factor IIH (TFIIH).The Journal of biological chemistry · 2017Article
- Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.Molecules (Basel, Switzerland) · 2017Review
- Pharmacologic ATM but not ATR kinase inhibition abrogates p21-dependent G1 arrest and promotes gastrointestinal syndrome after total body irradiation.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
ATR (ataxia telangiectasia and Rad-3-related) is a protein kinase that maintains genome stability and halts cell cycle phase transitions in response to DNA lesions that block DNA polymerase movement. These DNA replication-associated features of ATR function have led to the emergence of ATR kinase inhibitors as potential adjuvants for DNA-damaging cancer chemotherapeutics. However, whether ATR affects the genotoxic stress response in non-replicating, non-cycling cells is currently unknown. We therefore used chemical inhibition of ATR kinase activity to examine the role of ATR in quiescent human cells. Although ATR inhibition had no obvious effects on the viability of non-cycling cells, inhibition of ATR partially protected non-replicating cells from the lethal effects of UV and UV mimetics. Analyses of various DNA damage response signaling pathways demonstrated that ATR inhibition reduced the activation of apoptotic signaling by these agents in non-cycling cells. The pro-apoptosis/cell death function of ATR is likely due to transcription stress because the lethal effects of compounds that block RNA polymerase movement were reduced in the presence of an ATR inhibitor. These results therefore suggest that whereas DNA polymerase stalling at DNA lesions activates ATR to protect cell viability and prevent apoptosis, the stalling of RNA polymerases instead activates ATR to induce an apoptotic form of cell death in non-cycling cells. These results have important implications regarding the use of ATR inhibitors in cancer chemotherapy regimens.
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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.