ArticleeLife2018
p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic RAD52 and POLθ pathways.
Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 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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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
69 citing papers in PubMed, 87 citations in OpenAlex.
- Molecular landscape and clinical translation of DNA damage response alterations in solid tumors: A pan-cancer perspective on precision oncology.Neoplasia (New York, N.Y.) · 2026Review
- DPY30 Is an Epigenetic Decoupler Linking Replication Stress to Immunoediting in Pancreatic Cancer.Cancer research · 2026Article
- Synthetic lethality of decitabine plus ATR inhibition for TP53-mutated AML.Blood advances · 2026Article
- RF-SIRF reveals a replication stress-specific epigenetic code by spatio-temporal mapping of reversed forks.Nature communications · 2026Article
- The Zinc Finger Ran-Binding Protein 3 (ZRANB3): An Advanced Perspective.International journal of molecular sciences · 2026Review
- Mutant p53 variants differentially impact replication initiation and activate cGAS-STING to affect immune checkpoint inhibition.Communications biology · 2025Article
- Specific TP53 mutations impair the recruitment of 53BP1 to DNA double-strand breaks underlying the mechanism of radioresistance.European biophysics journal : EBJ · 2025Article
- RAD51 is chromatin enriched and targetable in BRCA1-deficient cells.Molecular cell · 2025Article
- A homozygous TRIP13 pathogenic variant associated with familiar oocyte arrest and prematurely condensed sperm chromosomes.Molecular cytogenetics · 2025Article
- Review
- Correlation of heat shock protein 1 expression with progression and prognosis of non-small cell lung cancer.Frontiers in oncology · 2025Article
- p53-dependent crosstalk between DNA replication integrity and redox metabolism mediated through a NRF2-PARP1 axis.Nucleic acids research · 2024Article
- R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.Acta biochimica et biophysica Sinica · 2024Article
- ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma.Nature communications · 2024Article
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer.Cancer communications (London, England) · 2024Article
- Nucleoside supplements as treatments for mitochondrial DNA depletion syndrome.Frontiers in cell and developmental biology · 2024Article
- Molecular mechanism of PARP inhibitor resistance.Oncoscience · 2024Review
- Mechanisms of synthetic lethality between BRCA1/2 and 53BP1 deficiencies and DNA polymerase theta targeting.Nature communications · 2023Article
- R-Loops in Genome Instability and Cancer.Cancers · 2023Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell cycle arrest. Yet, replication-mediated genomic instability is integral to oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By delineating human and murine separation-of-function p53 alleles, we find that p53 null and gain-of-function (GOF) mutations exhibit defects in restart of stalled or damaged DNA replication forks that drive genomic instability, which isgenetically separable from transcription activation. By assaying protein-DNA fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of MRE11 DNA replication restart nuclease. Importantly, p53 defects or depletion unexpectedly allow mutagenic RAD52 and POLθ pathways to hijack stalled forks, which we find reflected in p53 defective breast-cancer patient COSMIC mutational signatures. These data uncover p53 as a keystone regulator of replication homeostasis within a DNA restart network. Mechanistically, this has important implications for development of resistance in cancer therapy. Combined, these results define an unexpected role for p53-mediated suppression of replication genome instability.
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What OpenQuestion holds
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.