ArticleMolecular and cellular biology2011
Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 71 citations in OpenAlex.
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- Nuclear DAB2IP regulates DNA replication initiation through activating PLK1-mediated HBO1 phosphorylation.Nucleic acids research · 2025Article
- Proteins involved in cell division have broad developmental functions.Developmental biology · 2025Article
- Multi-Omic Evaluation of PLK1 Inhibitor-Onvansertib-In Colorectal Cancer Spheroids.Journal of mass spectrometry : JMS · 2025Article
- Dual DNA replication modes: varying fork speeds and initiation rates within the spatial replication program in Xenopus.Nucleic acids research · 2025Article
- Clinical relevance of PLK1 in epithelial ovarian cancer.Frontiers in pharmacology · 2025Review
- Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression.Cell death & disease · 2024Article
- PLK1 maintains DNA methylation and cell viability by regulating phosphorylation-dependent UHRF1 protein stability.Cell death discovery · 2023Article
- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Recent Progress on the Localization of PLK1 to the Kinetochore and Its Role in Mitosis.International journal of molecular sciences · 2022Review
- Polo-like kinase 1 (Plk1) regulates DNA replication origin firing and interacts with Rif1 in Xenopus.Nucleic acids research · 2021Article
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- Bioinformatics analysis of key genes in triple negative breast cancer and validation of oncogene PLK1.Annals of translational medicine · 2020Article
- The CINs of Polo-Like Kinase 1 in Cancer.Cancers · 2020Review
- Polo-like kinase 1 (Plk1) is a positive regulator of DNA replication in theCell cycle (Georgetown, Tex.) · 2020Article
- Novel candidate biomarkers of origin recognition complex 1, 5 and 6 for survival surveillance in patients with hepatocellular carcinoma.Journal of Cancer · 2020Article
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- Investigation of expressions of PDK1, PLK1 and c-Myc in diffuse large B-cell lymphoma.International journal of experimental pathology · 2019Article
- Cell cycle-resolved chromatin proteomics reveals the extent of mitotic preservation of the genomic regulatory landscape.Nature communications · 2018Article
- Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Polo-like kinase 1 (Plk1) plays pivotal roles in mitosis; however, little is known about its function in S phase. In this study, we show that inhibition of Plk1 impairs DNA replication and results in slow S-phase progression in cultured cancer cells. We have identified origin recognition complex 2 (Orc2), a member of the DNA replication machinery, as a Plk1 substrate and have shown that Plk1 phosphorylates Orc2 at Ser188 in vitro and in vivo. Furthermore, Orc2-S188 phosphorylation is enhanced when DNA replication is under challenge induced by ultraviolet, hydroxyurea, gemcitabine, or aphidicolin treatment. Cells expressing the unphosphorylatable mutant (S188A) of Orc2 had defects in DNA synthesis under stress, suggesting that this phosphorylation event is critical to maintain DNA replication under stress. To dissect the mechanism pertinent to this observation, we showed that Orc2-S188 phosphorylation associates with DNA replication origin and that cells expressing Orc2-S188A mutant fail to maintain the functional pre-replicative complex (pre-RC) under DNA replication stress. Furthermore, the intra-S-phase checkpoint is activated in Orc2-S188A-expressing cells to cause delay of S-phase progress. Our study suggests a novel role of Plk1 in facilitating DNA replication under conditions of stress to maintain genomic integrity.
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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.