ArticleNeoplasia (New York, N.Y.)2018
Inactivation of PRIM1 Function Sensitizes Cancer Cells to ATR and CHK1 Inhibitors.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 41 citations in OpenAlex.
- Machine learning-guided multimodal profiling defines perturbed immune states at the time of cancer diagnosis.Briefings in bioinformatics · 2026Article
- Targeting synthetic lethality in colorectal cancer.Chinese medical journal · 2025Article
- New Progress on DNA Primase Subunit Enzymes Research and Link to Cancer Development and Treatment Approaches.Current cancer drug targets · 2025Review
- The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer.Molecular oncology · 2024Article
- Harnessing DNA replication stress to target RBM10 deficiency in lung adenocarcinoma.Nature communications · 2024Article
- Isogenic Cell Lines Derived from Specific Organ Metastases Exhibit Divergent Cytogenomic Aberrations.Cancers · 2023Article
- Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance.NAR cancer · 2022Article
- ATR Inhibitors in Platinum-Resistant Ovarian Cancer.Cancers · 2022Review
- Article
- Sensitivity of cells to ATR and CHK1 inhibitors requires hyperactivation of CDK2 rather than endogenous replication stress or ATM dysfunction.Scientific reports · 2021Article
- DNA primase subunit 1 deteriorated progression of hepatocellular carcinoma by activating AKT/mTOR signaling and UBE2C-mediated P53 ubiquitination.Cell & bioscience · 2021Article
- Analysis of core genes for colorectal cancer prognosis based on immune and stromal scores.PeerJ · 2021Article
- The POLD1Scientific reports · 2020Article
- DNA Primase Subunit 1 Expression in Hepatocellular Carcinoma and Its Clinical Implication.BioMed research international · 2020Article
- Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine.ACS chemical biology · 2019Article
- Profiling the Mutational Landscape in Known Driver Genes and Novel Genes in African American Non-Small Cell Lung Cancer Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The phosphoinositide 3-kinase-related kinase ATR is a central regulator of the DNA damage response. Its chemical inhibition eliminates subsets of cancer cells in various tumor types. This effect is caused at least partly by the synthetically lethal relationship between ATR and certain DNA repair genes. In a previous screen using an siRNA library against DNA repair genes, we identified PRIM1, a part of the polymerase α-primase complex, as acting synthetically lethal with ATR. Applying a genetic ATR knock-in model of colorectal cancer cells, we confirmed that PRIM1 depletion inhibited proliferation of ATR-deficient cells and excluded artifacts due to clonal variation using an ATR reexpressing cell clone. We expanded these data by demonstrating in different cell lines that also chemical inhibition of ATR or its main effector kinase CHK1 reduces proliferation upon depletion of PRIM1. Mechanistically, PRIM1 depletion in ATR-deficient cells caused S-phase stasis in the absence of increased DNA damage followed by Wee1-mediated activation of caspase 8 and apoptosis. As PRIM1 inactivation sensitizes cancer cells to ATR and CHK1 inhibitors, mutations in PRIM1 or other components of the polymerase α-primase complex could represent novel targets for individualized tumor therapeutic approaches using ATR/CHK1 inhibitors, as has been previously demonstrated for POLD1, the catalytic subunit of polymerase δ.
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