ArticleCurrent biology : CB2010
Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation.
Article in Current biology : CB, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 100 citations in OpenAlex.
- Screening anticancer peptides performance in organotypic prostate tumor-stroma 3D models.International journal of cancer · 2026Article
- CAVPENET Peptide Inhibits Prostate Cancer Cells Proliferation and Migration through PP1γ-Dependent Inhibition of AKT Signaling.Pharmaceutics · 2024Article
- The eEF2 kinase coordinates the DNA damage response to cisplatin by supporting p53 activation.Cell death & disease · 2024Article
- PPP1R81 correlates with the survival and cell proliferation in lower-grade glioma.Bioscience reports · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- A pan-cancer analysis reveals the diagnostic and prognostic role of CDCA2 in low-grade glioma.PloS one · 2023Article
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- Cell Division Cycle-Associated Genes Are Potential Immune Regulators in Nasopharyngeal Carcinoma.Frontiers in oncology · 2022Article
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- Identification of a 5-Nutrient Stress-Sensitive Gene Signature to Predict Survival for Colorectal Cancer.BioMed research international · 2022Article
- CDCA2 Promotes HCC Cells Development via AKT-mTOR Pathway.Analytical cellular pathology (Amsterdam) · 2022Article
- The MASTL-ENSA-PP2A/B55 axis modulates cisplatin resistance in oral squamous cell carcinoma.Frontiers in cell and developmental biology · 2022Article
- The Sm core components of small nuclear ribonucleoproteins promote homologous recombination repair.DNA repair · 2021Article
- CDCA2 promotes tumorigenesis and induces radioresistance in oesophageal squamous cell carcinoma cells.Molecular medicine reports · 2021Article
- The roles of the cell division cycle-associated gene family in hepatocellular carcinoma.Journal of gastrointestinal oncology · 2021Article
- Increased CDCA2 Level Was Related to Poor Prognosis in Hepatocellular Carcinoma and Associated With Up-Regulation of Immune Checkpoints.Frontiers in medicine · 2021Article
- Article
- Aurora B regulates PP1γ-Repo-Man interactions to maintain the chromosome condensation state.The Journal of biological chemistry · 2020Article
- ATM-associated signalling triggers the unfolded protein response and cell death in response to stress.Communications biology · 2020Article
- Polo-like kinase 1 (Plk1) is a positive regulator of DNA replication in theCell cycle (Georgetown, Tex.) · 2020Article
6 more citing papers are in PubMed but not listed here.
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
backgroundIn response to DNA damage, cells activate checkpoints to halt cell-cycle progression and prevent genomic instability. Checkpoint activation induced by DNA double-strand breaks (DSB) is dependent on the ATM kinase, a master regulator of the DNA damage response (DDR) that is activated through autophosphorylation and monomerization.
resultsHere we show that either protein phosphatase 1 or 2A is sufficient to suppress activation of the DDR and that simultaneous inhibition of both phosphatases fully activates the response. PP1-dependent DDR regulation is mediated by its chromatin-targeting subunit, Repo-Man. Studies in Xenopus egg extracts demonstrate that Repo-Man interacts with ATM and PP1 through distinct domains, leading to PP1-dependent regulation of ATM phosphorylation and activation. Consequently, the level of Repo-Man determines the activation threshold of the DNA damage checkpoint. Repo-Man interacts and extensively colocalizes with ATM in human cells. Expression of wild-type, but not PP1 binding-deficient, Repo-Man attenuates DNA damage-induced ATM activation. Moreover, Repo-Man dissociates from active ATM at DNA damage sites, suggesting that activation of the DDR involves removal of inhibitory regulators. Analysis of primary tumor tissues and cell lines demonstrates that Repo-Man is frequently upregulated in many types of cancers. Elevated Repo-Man expression blunts DDR activation in precancerous cells, whereas knockdown of Repo-Man in malignant cancer cells resensitizes the DDR and restrains growth in soft agar.
conclusionsWe report essential DDR regulation mediated by Repo-Man-PP1 and further delineate underlying mechanisms. Moreover, our evidence suggests that elevated Repo-Man contributes to cancer progression.
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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.