ArticlePLoS biology2010
A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 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
147 citing papers in PubMed, 228 citations in OpenAlex.
- Bora, CEP192 and Cenexin regulate distinct Plk1-dependent cell and centrosome cycle transitions.Nature communications · 2026Article
- Zeste White 10 May Serve as a Prognostic Biomarker and Therapeutic Target for Human Breast Cancer.Breast cancer : basic and clinical research · 2026Article
- DNA double-strand break end resection factors and WRN facilitate mitotic DNA synthesis in human cells.Nature communications · 2025Article
- Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex.Nature communications · 2025Article
- Review
- Polo-like kinase inhibitors increase AAV production by halting cell cycle progression.Molecular therapy. Methods & clinical development · 2025Article
- Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation.Nature communications · 2024Article
- A TRilogy of ATR's Non-Canonical Roles Throughout the Cell Cycle and Its Relation to Cancer.Cancers · 2024Review
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).Nature communications · 2024Article
- 53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR).bioRxiv : the preprint server for biology · 2024Article
- G2 arrest primes hematopoietic stem cells for megakaryopoiesis.Cell reports · 2024Article
- Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination.Nature communications · 2024Article
- Broken chromosomes heading into mitosis: More than one way to patch a flat tire.The Journal of cell biology · 2024Review
- Control of cell proliferation by memories of mitosis.Science (New York, N.Y.) · 2024Article
- Distinct characteristics of the DNA damage response in mammalian oocytes.Experimental & molecular medicine · 2024Review
- PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability.EMBO reports · 2023Article
- POLQ to the rescue for double-strand break repair during mitosis.Nature structural & molecular biology · 2023Article
- Hornerin mediates phosphorylation of the polo-box domain in Plk1 by Chk1 to induce death in mitosis.Cell death and differentiation · 2023Article
- Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes.Nucleic acids research · 2023Article
- Chromosomal instability and its effect on cell lines.Cancer reports (Hoboken, N.J.) · 2023Review
87 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
16 authors at 6 institutions in 3 countries.
Funding
Abstract
DNA damage checkpoints arrest cell cycle progression to facilitate DNA repair. The ability to survive genotoxic insults depends not only on the initiation of cell cycle checkpoints but also on checkpoint maintenance. While activation of DNA damage checkpoints has been studied extensively, molecular mechanisms involved in sustaining and ultimately inactivating cell cycle checkpoints are largely unknown. Here, we explored feedback mechanisms that control the maintenance and termination of checkpoint function by computationally identifying an evolutionary conserved mitotic phosphorylation network within the DNA damage response. We demonstrate that the non-enzymatic checkpoint adaptor protein 53BP1 is an in vivo target of the cell cycle kinases Cyclin-dependent kinase-1 and Polo-like kinase-1 (Plk1). We show that Plk1 binds 53BP1 during mitosis and that this interaction is required for proper inactivation of the DNA damage checkpoint. 53BP1 mutants that are unable to bind Plk1 fail to restart the cell cycle after ionizing radiation-mediated cell cycle arrest. Importantly, we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells. Thus, a mitotic kinase-mediated negative feedback loop regulates the ATM-Chk2 branch of the DNA damage signaling network by phosphorylating conserved sites in 53BP1 and Chk2 to inactivate checkpoint signaling and control checkpoint duration.
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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.