ArticleJournal of cell science2019
An essential role for dNTP homeostasis following CDK-induced replication stress.
Article in Journal of cell science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- Elevated dNTP Pool Levels Impair Homologous Recombination and Enhance Glioblastoma Sensitivity to Irradiation and Temozolomide.International journal of molecular sciences · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Comprehensive multi-omics analysis reveals WEE1 as a synergistic lethal target with hyperthermia through CDK1 super-activation.Nature communications · 2024Article
- Article
- Structural and functional specificity of H3K36 methylation.Epigenetics & chromatin · 2022Review
- HREM, RNAseq and Cell Cycle Analyses Reveal the Role of the G2/M-Regulatory Protein, WEE1, on the Survivability of Chicken Embryos during Diapause.Biomedicines · 2022Article
- Expression of the cancer-associated DNA polymerase ε P286R in fission yeast leads to translesion synthesis polymerase dependent hypermutation and defective DNA replication.PLoS genetics · 2021Article
- Modeling Heterogeneity of Triple-Negative Breast Cancer Uncovers a Novel Combinatorial Treatment Overcoming Primary Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Exploiting Replication Stress as a Novel Therapeutic Intervention.Molecular cancer research : MCR · 2021Review
- Communication between Cyclin-dependent kinase Cdc2 and the Wis1-Spc1 MAPK pathway determines mitotic timing inBiology open · 2020Article
- mTOR inhibition overcomes primary and acquired resistance to Wee1 inhibition by augmenting replication stress in epithelial ovarian cancers.American journal of cancer research · 2020Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Replication stress is a common feature of cancer cells, and thus a potentially important therapeutic target. Here, we show that cyclin-dependent kinase (CDK)-induced replication stress, resulting from Wee1 inactivation, is synthetic lethal with mutations disrupting dNTP homeostasis in fission yeast. Wee1 inactivation leads to increased dNTP demand and replication stress through CDK-induced firing of dormant replication origins. Subsequent dNTP depletion leads to inefficient DNA replication, DNA damage and to genome instability. Cells respond to this replication stress by increasing dNTP supply through histone methyltransferase Set2-dependent MBF-induced expression of Cdc22, the catalytic subunit of ribonucleotide reductase (RNR). Disrupting dNTP synthesis following Wee1 inactivation, through abrogating Set2-dependent H3K36 tri-methylation or DNA integrity checkpoint inactivation results in critically low dNTP levels, replication collapse and cell death, which can be rescued by increasing dNTP levels. These findings support a 'dNTP supply and demand' model in which maintaining dNTP homeostasis is essential to prevent replication catastrophe in response to CDK-induced replication stress.
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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.