ArticleMolecular and cellular biology2007
p53 mediates senescence-like arrest induced by chronic replicational stress.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 80 citations in OpenAlex.
- Autophagy revealed as a targetable vulnerability in senescent cells by cell painting phenotypic profiling: a mechanistic study of MCOPPB and related compounds.GeroScience · 2026Article
- Genome homeostasis defects drive enlarged cells into senescence.Molecular cell · 2023Article
- Nociceptin/orphanin FQ opioid receptor (NOP) selective ligand MCOPPB links anxiolytic and senolytic effects.GeroScience · 2022Article
- Hydroxyurea Induces Bone Marrow Mesenchymal Stromal Cells Senescence and Modifies Cell Functionality In Vitro.Journal of personalized medicine · 2021Article
- Mechanisms of Hydroxyurea-Induced Cellular Senescence: An Oxidative Stress Connection?Oxidative medicine and cellular longevity · 2021Review
- Antioxidant Effect ofBioMed research international · 2021Article
- The DNA methylation of FOXO3 and TP53 as a blood biomarker of late-onset asthma.Journal of translational medicine · 2020Article
- Polyomavirus Small T Antigen Induces Apoptosis in Mammalian Cells through the UNC5B Pathway in a PP2A-Dependent Manner.Journal of virology · 2020Article
- Resistance to targeted therapies as a multifactorial, gradual adaptation to inhibitor specific selective pressures.Nature communications · 2020Article
- Convergence of therapy-induced senescence (TIS) and EMT in multistep carcinogenesis: current opinions and emerging perspectives.Cell death discovery · 2020Review
- Variable DNA methylation of aging-related genes is associated with male COPD.Respiratory research · 2019Article
- New Insights for Cellular and Molecular Mechanisms of Aging and Aging-Related Diseases: Herbal Medicine as Potential Therapeutic Approach.Oxidative medicine and cellular longevity · 2019Review
- Transcriptional activation of p21Oncotarget · 2018Article
- Article
- DNA replication stress and cancer chemotherapy.Cancer science · 2018Review
- Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress.Nucleic acids research · 2017Article
- A Small-Molecule Inhibitor of WEE1, AZD1775, Synergizes with Olaparib by Impairing Homologous Recombination and Enhancing DNA Damage and Apoptosis in Acute Leukemia.Molecular cancer therapeutics · 2017Article
- Review
- Small molecule compounds that induce cellular senescence.Aging cell · 2016Review
- Deoxyribonucleotide metabolism, mutagenesis and cancer.Nature reviews. Cancer · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Previous studies have shown that exposure of cells to high levels of replicational stress leads to permanent proliferation arrest that does not require p53. We have examined cellular responses to therapeutically relevant low levels of replicational stress that allow limited proliferation. Chronic exposure to low concentrations of hydroxyurea, aphidicolin, or etoposide induced irreversible cell cycle arrest after several population doublings. Inhibition of p53 activity antagonized this arrest and enhanced the long-term proliferation of p53 mutant cells. p21CIP1 was found to be a critical p53 target for arrest induced by hydroxyurea or aphidicolin, but not etoposide, as judged by the ability of p21CIP1 suppression to mimic the effects of p53 disruption. Suppression of Rad51 expression, required for homologous recombination repair, blocked the ability of mutant p53 to antagonize arrest induced by etoposide, but not aphidicolin. Thus, the ability of mutant p53 to prevent arrest induced by replicational stress per se is primarily dependent on preventing p21CIP1 up-regulation. However, when replication stress is associated with DNA strand breaks (such as with etoposide), up-regulation of homologous recombination repair in response to p53 disruption becomes important. Since replicational stress leads to clonal selection of cells with p53 mutations, our results highlight the potential importance of chronic replicational stress in promoting cancer development.
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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.