ArticleThe EMBO journal2010
Molecular architecture of the DNA replication origin activation checkpoint.
Article in The EMBO journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 52 citations in OpenAlex.
- CDC7 is a targetable regulator of advanced prostate cancer.Scientific reports · 2025Article
- FOXOs: masters of the equilibrium.The FEBS journal · 2022Review
- Lactate induces aberration in the miR-30a-DBF4 axis to promote the development of gastric cancer and weakens the sensitivity to 5-Fu.Cancer cell international · 2021Article
- A kinase inhibitor screen identifies a dual cdc7/CDK9 inhibitor to sensitise triple-negative breast cancer to EGFR-targeted therapy.Breast cancer research : BCR · 2019Article
- Cell division cycle 7 is a potential therapeutic target in oral squamous cell carcinoma and is regulated by E2F1.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Fructose 2,6-Bisphosphate in Cancer Cell Metabolism.Frontiers in oncology · 2018Review
- DDK Promotes Tumor Chemoresistance and Survival via Multiple Pathways.Neoplasia (New York, N.Y.) · 2017Article
- A novel p53-Cdc7 link induced by genotoxic stress.Cell cycle (Georgetown, Tex.) · 2017Article
- p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress.Cell cycle (Georgetown, Tex.) · 2016Article
- Cdc7 is a potent anti-cancer target in pancreatic cancer due to abrogation of the DNA origin activation checkpoint.Oncotarget · 2016Article
- Nuclear cytoplasmic trafficking of proteins is a major response of human fibroblasts to oxidative stress.Journal of proteome research · 2014Article
- Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging.The Journal of clinical investigation · 2014Article
- Extracellular signal-regulated kinase signaling-mediated induction and interaction of FOXO3a and p53 contribute to the inhibition of nasopharyngeal carcinoma cell growth by curcumin.International journal of oncology · 2014Article
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- Subcellular proteomics reveals a role for nucleo-cytoplasmic trafficking at the DNA replication origin activation checkpoint.Journal of proteome research · 2013Article
- Spatial distribution of cellular function: the partitioning of proteins between mitochondria and the nucleus in MCF7 breast cancer cells.Journal of proteome research · 2012Article
- Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells.Genes & development · 2012Article
- Mechanism of cancer cell death induced by depletion of an essential replication regulator.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Perturbation of DNA replication initiation arrests human cells in G1, pointing towards an origin activation checkpoint. We used RNAi against Cdc7 kinase to inhibit replication initiation and dissect this checkpoint in fibroblasts. We show that the checkpoint response is dependent on three axes coordinated through the transcription factor FoxO3a. In arrested cells, FoxO3a activates the ARF-∣Hdm2-∣p53 → p21 pathway and mediates p15(INK4B) upregulation; p53 in turn activates expression of the Wnt/β-catenin signalling antagonist Dkk3, leading to Myc and cyclin D1 downregulation. The resulting loss of CDK activity inactivates the Rb-E2F pathway and overrides the G1-S transcriptional programme. Fibroblasts concomitantly depleted of Cdc7/FoxO3a, Cdc7/p15, Cdc7/p53 or Cdc7/Dkk3 can bypass the arrest and proceed into an abortive S phase followed by apoptosis. The lack of redundancy between the checkpoint axes and reliance on several tumour suppressor proteins commonly inactivated in human tumours provides a mechanistic basis for the cancer-cell-specific killing observed with emerging Cdc7 inhibitors.
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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.