ArticleNucleic acids research2014
A gemcitabine sensitivity screen identifies a role for NEK9 in the replication stress response.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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
33 citing papers in PubMed, 43 citations in OpenAlex.
- A Phase I/II Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Low-Dose Gemcitabine in Patients with Advanced Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- GALNT1 drives aggressive phenotypes of rheumatoid synoviocytes via NEK9 O-glycosylation.JCI insight · 2026Article
- Ploidy shapes gemcitabine response through altered potency and delayed cell death.bioRxiv : the preprint server for biology · 2026Article
- Overexpression of the NEK8 kinase inhibits homologous recombination.DNA repair · 2025Article
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- NEK kinases in cell cycle regulation, DNA damage response, and cancer progression.Tissue & cell · 2025Review
- Cytidine deaminases APOBEC3C and APOBEC3D promote DNA replication stress resistance in pancreatic cancer cells.Nature cancer · 2024Article
- The pharmacoepigenomic landscape of cancer cell lines reveals the epigenetic component of drug sensitivity.Communications biology · 2023Article
- RETSAT associates with DDX39B to promote fork restarting and resistance to gemcitabine based chemotherapy in pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2022Article
- In Mitosis You Are Not: The NIMA Family of Kinases inInternational journal of molecular sciences · 2022Review
- mTORC2 regulates ribonucleotide reductase to promote DNA replication and gemcitabine resistance in non-small cell lung cancer.Neoplasia (New York, N.Y.) · 2021Article
- Article
- Review
- NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation.Theranostics · 2021Article
- Article
- EZH2 has a non-catalytic and PRC2-independent role in stabilizing DDB2 to promote nucleotide excision repair.Oncogene · 2020Article
- Article
- Regulator of Chromosome Condensation 2 Modulates Cell Cycle Progression, Tumorigenesis, and Therapeutic Resistance.Frontiers in molecular biosciences · 2020Review
- Genome-scale CRISPR/Cas9 screen determines factors modulating sensitivity to ProTide NUC-1031.Scientific reports · 2019Article
- Mass Spectrometry-Based Proteomics Reveals Potential Roles of NEK9 and MAP2K4 in Resistance to PI3K Inhibition in Triple-Negative Breast Cancers.Cancer research · 2018Article
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
The Replication Stress Response (RSR) is a signaling network that recognizes challenges to DNA replication and coordinates diverse DNA repair and cell-cycle checkpoint pathways. Gemcitabine is a nucleoside analogue that causes cytotoxicity by inducing DNA replication blocks. Using a synthetic lethal screen of a RNAi library of nuclear enzymes to identify genes that when silenced cause gemcitabine sensitization or resistance in human triple-negative breast cancer cells, we identified NIMA (never in mitosis gene A)-related kinase 9 (NEK9) as a key component of the RSR. NEK9 depletion in cells leads to replication stress hypersensitivity, spontaneous accumulation of DNA damage and RPA70 foci, and an impairment in recovery from replication arrest. NEK9 protein levels also increase in response to replication stress. NEK9 complexes with CHK1, and moreover, NEK9 depletion impairs CHK1 autophosphorylation and kinase activity in response to replication stress. Thus, NEK9 is a critical component of the RSR that promotes CHK1 activity, maintaining genome integrity following challenges to DNA replication.
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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.