ArticleThe Journal of biological chemistry2011
Studies on human DNA polymerase epsilon and GINS complex and their role in DNA replication.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Human DNA polymerase ε is a source of C>T mutations at CpG dinucleotides.Nature genetics · 2024Article
- Unprocessed genomic uracil as a source of DNA replication stress in cancer cells.Molecular cell · 2024Article
- Accelerated clinical response achieved by combining short-term tumor-directed photodynamic therapy with immunotherapy-based systemic therapies in synchronous colorectal cancer with MSI-H and POLE mutation: a case report.Frontiers in immunology · 2024Article
- A simple bypass assay for DNA polymerases shows that cancer-associated hypermutating variants exhibit differences in vitro.The FEBS journal · 2023Article
- Saccharomyces cerevisiae DNA polymerase IV overcomes Rad51 inhibition of DNA polymerase δ in Rad52-mediated direct-repeat recombination.Nucleic acids research · 2023Article
- Identification ofTranslational cancer research · 2023Article
- Article
- Overexpression of GINS4 is associated with poor prognosis and survival in glioma patients.Molecular medicine (Cambridge, Mass.) · 2021Article
- Expression of the cancer-associated DNA polymerase ε P286R in fission yeast leads to translesion synthesis polymerase dependent hypermutation and defective DNA replication.PLoS genetics · 2021Article
- Recombination and Pol ζ Rescue Defective DNA Replication upon Impaired CMG Helicase-Pol ε Interaction.International journal of molecular sciences · 2020Article
- Kinetic investigation of the polymerase and exonuclease activities of human DNA polymerase ε holoenzyme.The Journal of biological chemistry · 2020Article
- Structure of the polymerase ε holoenzyme and atomic model of the leading strand replisome.Nature communications · 2020Article
- GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel-like factor 4, promotes the growth of colorectal cancer.Cancer science · 2020Article
- POLE mutations improve the prognosis of endometrial cancer via regulating cellular metabolism through AMF/AMFR signal transduction.BMC medical genetics · 2019Article
- Defects in the GINS complex increase the instability of repetitive sequences via a recombination-dependent mechanism.PLoS genetics · 2019Article
- Psf3 as a possible biomarker of postoperative chemotherapy for patients with early pulmonary adenocarcinoma.Thoracic cancer · 2019Article
- POLE proofreading defects: Contributions to mutagenesis and cancer.DNA repair · 2019Review
- The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42.Theranostics · 2019Article
- Regulation of the initiation of DNA replication in human cells.DNA repair · 2018Review
- The HPV E2 Transcriptional Transactivation Protein Stimulates Cellular DNA Polymerase Epsilon.Viruses · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotic cells, DNA replication is carried out by the coordinated action of three DNA polymerases (Pols), Pol α, δ, and ε. In this report, we describe the reconstitution of the human four-subunit Pol ε and characterization of its catalytic properties in comparison with Pol α and Pol δ. Human Pol ε holoenzyme is a monomeric complex containing stoichiometric subunit levels of p261/Pol 2, p59, p17, and p12. We show that the Pol ε p261 N-terminal catalytic domain is solely responsible for its ability to catalyze DNA synthesis. Importantly, human Pol (hPol) ε was found more processive than hPol δ in supporting proliferating cell nuclear antigen-dependent elongation of DNA chains, which is in keeping with proposed roles for hPol ε and hPol δ in the replication of leading and lagging strands, respectively. Furthermore, GINS, a component of the replicative helicase complex that is composed of Sld5, Psf1, Psf2, and Psf3, was shown to interact weakly with all three replicative DNA Pols (α, δ, and ε) and to markedly stimulate the activities of Pol α and Pol ε. In vivo studies indicated that siRNA-targeted depletion of hPol δ and/or hPol ε reduced cell cycle progression and the rate of fork progression. Under the conditions used, we noted that depletion of Pol ε had a more pronounced inhibitory effect on cellular DNA replication than depletion of Pol δ. We suggest that reduction in the level of Pol δ may be less deleterious because of its collision-and-release role in lagging strand synthesis.
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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.