ArticleThe EMBO journal2019
Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Targeting common denominators of DNA damage tolerance mechanisms as therapeutic strategy to cope with dynamic phenotypic changes in triple-negative breast cancer cells.Cell death discovery · 2026Article
- RTF2 and CLASPIN localize CHK1 to the replication fork to control S-phase progression.Science advances · 2026Article
- Replication origin firing capacity indicates ATR inhibitor sensitivity.Nature communications · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Oncogenic YAP sensitizes cells to CHK1 inhibition via CDK4/6 driven G1 acceleration.EMBO reports · 2025Article
- Versatile enhancement of the killing potential of anti-cancer agents achieved by peptide mimetics of the PCNA interface towards specialized DNA polymerases.Cell death & disease · 2025Article
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- Transcription and DNA replication collisions lead to large tandem duplications and expose targetable therapeutic vulnerabilities in cancer.Nature cancer · 2024Article
- ATR kinase supports normal proliferation in the early S phase by preventing replication resource exhaustion.Nature communications · 2023Article
- Polymerase iota (Pol ι) prevents PrimPol-mediated nascent DNA synthesis and chromosome instability.Science advances · 2023Article
- Article
- Innate immunity mediator STING modulates nascent DNA metabolism at stalled forks in human cells.Frontiers in molecular biosciences · 2022Article
- A Catalytically Independent Function of Human DNA Polymerase Kappa Controls the Stability and Abundance of Checkpoint Kinase 1.Molecular and cellular biology · 2021Article
- Impact of the interplay between stemness features, p53 and pol iota on replication pathway choices.Nucleic acids research · 2021Article
- Targeting the PI3K/mTOR Pathway Augments CHK1 Inhibitor-Induced Replication Stress and Antitumor Activity in High-Grade Serous Ovarian Cancer.Cancer research · 2020Article
- Mus81-Eme1-dependent aberrant processing of DNA replication intermediates in mitosis impairs genome integrity.Science advances · 2020Article
- Article
- Inducible SMARCAL1 knockdown in iPSC reveals a link between replication stress and altered expression of master differentiation genes.Disease models & mechanisms · 2019Article
- Chk1 loss creates replication barriers that compromise cell survival independently of excess origin firing.The EMBO journal · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
The effectiveness of checkpoint kinase 1 (Chk1) inhibitors at killing cancer cells is considered to be fully dependent on their effect on DNA replication initiation. Chk1 inhibition boosts origin firing, presumably limiting the availability of nucleotides and in turn provoking the slowdown and subsequent collapse of forks, thus decreasing cell viability. Here we show that slow fork progression in Chk1-inhibited cells is not an indirect effect of excess new origin firing. Instead, fork slowdown results from the accumulation of replication barriers, whose bypass is impeded by CDK-dependent phosphorylation of the specialized DNA polymerase eta (Polη). Also in contrast to the linear model, the accumulation of DNA damage in Chk1-deficient cells depends on origin density but is largely independent of fork speed. Notwithstanding this, origin dysregulation contributes only mildly to the poor proliferation rates of Chk1-depleted cells. Moreover, elimination of replication barriers by downregulation of helicase components, but not their bypass by Polη, improves cell survival. Our results thus shed light on the molecular basis of the sensitivity of tumors to Chk1 inhibition.
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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.