ArticleOncogenesis2021
Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours.
Article in Oncogenesis, 2021. 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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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Expanding Synthetic Lethality in DNA Damage Response-Defective Cancers Through Stress Phenotype-Guided Kinase Targeting.International journal of molecular sciences · 2026Review
- [Preliminary investigation into the mechanisms of thalidomide in inhibiting the malignant transformation of oral leukoplakia].Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2026Article
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Network-based discovery of gene-miRNA interactions associated with hepatocellular carcinoma.Irish journal of medical science · 2026Article
- Integrative Transcriptomics, Machine Learning, and Molecular Dynamics Reveal Honghua Longdan (ACS omega · 2026Article
- Molecular profiling of primary versus paired asynchronous metastatic clear cell renal cell carcinoma reveals heterogeneity in tumor immune microenvironment.Scientific reports · 2026Article
- From survival of irradiated mice to modern molecular insights: a seventy-year journey in radiobiology at the institute of biophysics, Czech academy of sciences.European biophysics journal : EBJ · 2025Review
- KMT2C inactivation leads to PTEN downregulation and tolerance to DNA damage during cell cycle progression.NPJ precision oncology · 2025Article
- Molecular Profiling of Primary versus Paired Asynchronous Metastatic Clear Cell Renal Cell Carcinoma Reveals Heterogeneity in Tumor Immune Microenvironment.Research square · 2025Article
- The Impact of Major and Minor Phytocannabinoids on the Maintenance and Function of INS-1 β-Cells Under High-Glucose and High-Lipid Conditions.Molecules (Basel, Switzerland) · 2025Article
- Unleashing the potential of Genistein and its derivatives as effective therapeutic agents for breast cancer treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Article
- Harnessing the interaction between redox signaling and senescence to restrain tumor drug resistance.Frontiers in cell and developmental biology · 2025Review
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- Neutrophil elastase (Elane) may serve as a potential therapeutic target in inflammatory bowel disease-associated growth attenuation: focus on the epiphyseal growth plate in young male rats.Frontiers in endocrinology · 2025Article
- Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The role of Aurora kinase A in hepatocellular carcinoma: Unveiling the intriguing functions of a key but still underexplored factor in liver cancer.Cell proliferation · 2024Review
- Centrosomes and associated proteins in pathogenesis and treatment of breast cancer.Frontiers in oncology · 2024Review
- Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation.Cell death discovery · 2023Article
- The role of radiotherapy-related autophagy genes in the prognosis and immune infiltration in lung adenocarcinoma.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defective DNA repair is being demonstrated to be a useful target in cancer treatment. Currently, defective repair is identified by specific gene mutations, however defective repair is a common feature of cancers without these mutations. DNA damage triggers cell cycle checkpoints that are responsible for co-ordinating cell cycle arrest and DNA repair. Defects in checkpoint signalling components such as ataxia telangiectasia mutated (ATM) occur in a low proportion of cancers and are responsible for reduced DNA repair and increased genomic instability. Here we have investigated the AURKA-PLK1 cell cycle checkpoint recovery pathway that is responsible for exit from the G2 phase cell cycle checkpoint arrest. We demonstrate that dysregulation of PP6 and AURKA maintained elevated PLK1 activation to promote premature exit from only ATM, and not ATR-dependent checkpoint arrest. Surprisingly, depletion of the B55α subunit of PP2A that negatively regulates PLK1 was capable of overcoming ATM and ATR checkpoint arrests. Dysregulation of the checkpoint recovery pathway reduced S/G2 phase DNA repair efficiency and increased genomic instability. We found a strong correlation between dysregulation of the PP6-AURKA-PLK1-B55α checkpoint recovery pathway with signatures of defective homologous recombination and increased chromosomal instability in several cancer types. This work has identified an unrealised source of G2 phase DNA repair defects and chromosomal instability that are likely to be sensitive to treatments targeting defective repair.
Identifiers
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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.