ArticleCell cycle (Georgetown, Tex.)2014
Depletion of ATR selectively sensitizes ATM-deficient human mammary epithelial cells to ionizing radiation and DNA-damaging agents.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Advances in Targeted Therapy for Metastatic Prostate Cancer.Current treatment options in oncology · 2025Review
- ATM in immunobiology: From lymphocyte development to cancer immunotherapy.Translational oncology · 2025Review
- Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.Frontiers in oncology · 2025Review
- ASPM promotes ATR-CHK1 activation and stabilizes stalled replication forks in response to replication stress.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 'Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics'.Frontiers in molecular biosciences · 2022Review
- Mechanisms of Cancer Cell Death: Therapeutic Implications for Pancreatic Ductal Adenocarcinoma.Cancers · 2021Review
- Review
- Pharmacological inhibition of ataxia-telangiectasia mutated exacerbates acute kidney injury by activating p53 signaling in mice.Scientific reports · 2020Article
- Targeting DNA repair in cancer: current state and novel approaches.Cellular and molecular life sciences : CMLS · 2020Review
- Ataxia telangiectasia and Rad3-related inhibitors and cancer therapy: where we stand.Journal of hematology & oncology · 2019Review
- Selective Autophagy Regulates Cell Cycle in Cancer Therapy.Theranostics · 2019Review
- SPOP regulates the DNA damage response and lung adenocarcinoma cell response to radiation.American journal of cancer research · 2019Article
- Low ATM expression and progression-free and overall survival in advanced gastric cancer patients treated with first-line XELOX chemotherapy.Journal of gastrointestinal oncology · 2018Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Insight into the role of PIKK family members and NF-кB in DNAdamage-induced senescence and senescence-associated secretory phenotype of colon cancer cells.Cell death & disease · 2018Article
- Directing the use of DDR kinase inhibitors in cancer treatment.Expert opinion on investigational drugs · 2017Review
- Precision medicine for metastatic breast cancer--limitations and solutions.Nature reviews. Clinical oncology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
DNA damage response (DDR) to double strand breaks is coordinated by 3 phosphatidylinositol 3-kinase-related kinase (PIKK) family members: the ataxia-telangiectasia mutated kinase (ATM), the ATM and Rad3-related (ATR) kinase and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). ATM and ATR are central players in activating cell cycle checkpoints and function as an active barrier against genome instability and tumorigenesis in replicating cells. Loss of ATM function is frequently reported in various types of tumors, thus placing more reliance on ATR for checkpoint arrest and cell survival following DNA damage. To investigate the role of ATR in the G2/M checkpoint regulation in response to ionizing radiation (IR), particularly when ATM is deficient, cell lines deficient of ATM, ATR, or both were generated using a doxycycline-inducible lentiviral system. Our data suggests that while depletion of ATR or ATM alone in wild-type human mammary epithelial cell cultures (HME-CCs) has little effect on radiosensitivity or IR-induced G2/M checkpoint arrest, depletion of ATR in ATM-deficient cells causes synthetic lethality following IR, which correlates with severe G2/M checkpoint attenuation. ATR depletion also inhibits IR-induced autophagy, regardless of the ATM status, and enhances IR-induced apoptosis particularly when ATM is deficient. Collectively, our results clearly demonstrate that ATR function is required for the IR-induced G2/M checkpoint activation and subsequent survival of cells with ATM deficiency. The synthetic lethal interaction between ATM and ATR in response to IR supports ATR as a therapeutic target for improved anti-cancer regimens, especially in tumors with a dysfunctional ATM pathway.
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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.