ArticleOncogene2017
Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Identification of RRM2 as a key regulator of malignant epithelial cells in gastric cancer through single‑cell transcriptomics.Oncology reports · 2026Article
- Decoding nucleoside supplementation: how thymidine outperforms ribonucleosides in accelerating mammalian replication forks.Nucleic acids research · 2025Article
- SHMT2 is essential for mammalian preimplantation embryonic development throughMolecular therapy. Nucleic acids · 2025Article
- Embryonic stem cells maintain high origin activity and slow forks to coordinate replication with cell cycle progression.EMBO reports · 2024Article
- Rothmund-Thomson syndrome, a disorder far from solved.Frontiers in aging · 2023Review
- Article
- Efficient terminal erythroid differentiation requires the APC/C cofactor Cdh1 to limit replicative stress in erythroblasts.Scientific reports · 2022Article
- APC/C ubiquitin ligase: Functions and mechanisms in tumorigenesis.Seminars in cancer biology · 2020Review
- Review
- A user-friendly, high-throughput tool for the precise fluorescent quantification of deoxyribonucleoside triphosphates from biological samples.Nucleic acids research · 2020Article
- A Survey of Essential Genome Stability Genes Reveals That Replication Stress Mitigation Is Critical for Peri-Implantation Embryogenesis.Frontiers in cell and developmental biology · 2020Review
- The role of dNTP metabolites in control of the embryonic cell cycle.Cell cycle (Georgetown, Tex.) · 2019Review
- CD98hc (SLC3A2) sustains amino acid and nucleotide availability for cell cycle progression.Scientific reports · 2019Article
- Everything in Moderation: Lessons Learned by Exploiting Moderate Replication Stress in Cancer.Cancers · 2019Review
- Down-regulation of Cdk1 activity in G1 coordinates the G1/S gene expression programme with genome replication.Current genetics · 2019Review
- Activating the Anaphase Promoting Complex to Enhance Genomic Stability and Prolong Lifespan.International journal of molecular sciences · 2018Review
- Chromatin conformation regulates the coordination between DNA replication and transcription.Nature communications · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The APC/C-Cdh1 ubiquitin-ligase complex targets cell cycle regulators for proteosomal degradation and helps prevent tumor development and accumulation of chromosomal aberrations. Replication stress has been proposed to be the main driver of genomic instability in the absence of Cdh1, but the real contribution of APC/C-Cdh1 to efficient replication, especially in normal cells, remains unclear. Here we show that, in primary MEFs, acute depletion or permanent ablation of Cdh1 slowed down replication fork movement and increased origin activity. Partial inhibition of origin firing does not accelerate replication forks, suggesting that fork progression is intrinsically limited in the absence of Cdh1. Moreover, exogenous supply of nucleotide precursors, or ectopic overexpression of RRM2, the regulatory subunit of Ribonucleotide Reductase, restore replication efficiency, indicating that dNTP availability could be impaired upon Cdh1 loss. Indeed, we found reduced dNTP levels in Cdh1-deficient MEFs. Importantly, DNA breakage is also significantly alleviated by increasing intracellular dNTP pools, strongly suggesting that genomic instability is the result of aberrant replication. These observations highlight the relevance of APC/C-Cdh1 activity during G1 to ensure an adequate supply of dNTPs to the replisome, prevent replication stress and the resulting chromosomal breaks and, ultimately, suppress tumorigenesis.
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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.