ArticleThe EMBO journal2004
ATR functions as a gene dosage-dependent tumor suppressor on a mismatch repair-deficient background.
Article in The EMBO journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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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
59 citing papers in PubMed, 111 citations in OpenAlex.
- Claspin and Cancer: Where Are We Now?International journal of molecular sciences · 2025Review
- Article
- Profiling genetic mutations in the DNA damage repair genes of oral squamous cell carcinoma patients from Pakistan.Scientific reports · 2025Article
- Radiotherapy resistance driven by Asparagine endopeptidase through ATR pathway modulation in breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Inflammasome protein scaffolds the DNA damage complex during tumor development.Nature immunology · 2024Article
- Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis.Genes & development · 2024Article
- A microglia clonal inflammatory disorder in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Implications of ubiquitination and the maintenance of replication fork stability in cancer therapy.Bioscience reports · 2023Review
- An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress.Nature communications · 2023Article
- Could Inhibiting the DNA Damage Repair Checkpoint Rescue Immune-Checkpoint-Inhibitor-Resistant Endometrial Cancer?Journal of clinical medicine · 2023Review
- [The role of the response to DNA damage in granulomatous diseases].Zeitschrift fur Rheumatologie · 2022Article
- DNA repair defects in cancer and therapeutic opportunities.Genes & development · 2022Review
- LAP2α preserves genome integrity through assisting RPA deposition on damaged chromatin.Genome biology · 2022Article
- RBMX is required for activation of ATR on repetitive DNAs to maintain genome stability.Cell death and differentiation · 2020Article
- Somatic genetic aberrations in benign breast disease and the risk of subsequent breast cancer.NPJ breast cancer · 2020Article
- Overexpression of Claspin and Timeless protects cancer cells from replication stress in a checkpoint-independent manner.Nature communications · 2019Article
- Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA.Nature communications · 2018Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- Impact of Age and Insulin-Like Growth Factor-1 on DNA Damage Responses in UV-Irradiated Human Skin.Molecules (Basel, Switzerland) · 2017Review
- Insulin-like Growth Factor 1 Receptor Signaling Is Required for Optimal ATR-CHK1 Kinase Signaling in Ultraviolet B (UVB)-irradiated Human Keratinocytes.The Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ataxia-telangiectasia mutated and rad3-related (ATR) kinase orchestrates cellular responses to DNA damage and replication stress. Complete loss of ATR function leads to chromosomal instability and cell death. However, heterozygous ATR mutations are found in human cancers with microsatellite instability, suggesting that ATR haploinsufficiency contributes to tumorigenesis. To test this possibility, we generated human cell line and mouse model systems in which a single ATR allele was inactivated on a mismatch repair (MMR)-deficient background. Monoallelic ATR gene targeting in MLH1-deficient HCT 116 colon carcinoma cells resulted in hypersensitivity to genotoxic stress accompanied by dramatic increases in fragile site instability, and chromosomal amplifications and rearrangements. The ATR(+/-) HCT 116 cells also displayed compromised activation of Chk1, an important downstream target for ATR. In complementary studies, we demonstrated that mice bearing the same Atr(+/-)/Mlh1(-/-) genotype were highly prone to both embryonic lethality and early tumor development. These results demonstrate that MMR proteins and ATR functionally interact during the cellular response to genotoxic stress, and that ATR serves as a haploinsufficient tumor suppressor in MMR-deficient cells.
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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.