ArticleNature communications2020
Structure of the polymerase ε holoenzyme and atomic model of the leading strand replisome.
Article in Nature communications, 2020. 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, 82 citations in OpenAlex.
- Pan-cancer multi-omics analysis reveals upregulation of the POLE2 subunit of DNA polymerase epsilon and its associations with patient survival and cellular pathways beyond DNA replication.NAR genomics and bioinformatics · 2026Article
- Deficiency in POLE Exonuclease Causes Synthetic Lethality in Highly Aneuploid Cancer Cells.Cancer research · 2026Article
- Pol γ possesses separate metal binding sites for polymerase and strand displacement functions.Nucleic acids research · 2026Article
- The genetic and biochemical basis of human leading strand synthesis.Nature communications · 2025Article
- Evidence for a functional interaction between yeast Pol ε and PCNA in vivo.Nucleic acids research · 2025Article
- Faithful inheritance: Parental histone recycling and epigenetic memory in fission yeast.Cell insight · 2025Review
- The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Replicative DNA polymerase epsilon and delta holoenzymes show wide-ranging inhibition at G-quadruplexes in the human genome.Nucleic acids research · 2025Article
- A conserved thumb domain insertion in DNA polymerase epsilon supports processive DNA synthesis.Nucleic acids research · 2025Article
- Site directed mutagenesis reveals functional importance of conserved amino acid residues within the N-terminal domain of Dpb2 in budding yeast.Archives of microbiology · 2024Article
- Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε.Nature structural & molecular biology · 2024Article
- Molecular mechanism of parental H3/H4 recycling at a replication fork.Nature communications · 2024Article
- Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structures of the human leading strand Polε-PCNA holoenzyme.Nature communications · 2024Article
- Mrc1 regulates parental histone segregation and heterochromatin inheritance.Molecular cell · 2024Article
- Single-molecule characterization of SV40 replisome and novel factors: human FPC and Mcm10.Nucleic acids research · 2024Article
- Review
- Mechanism of PCNA loading by Ctf18-RFC for leading-strand DNA synthesis.Science (New York, N.Y.) · 2024Article
- Structural and biochemical characterization of the mitomycin C repair exonuclease MrfB.Nucleic acids research · 2024Article
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The eukaryotic leading strand DNA polymerase (Pol) ε contains 4 subunits, Pol2, Dpb2, Dpb3 and Dpb4. Pol2 is a fusion of two B-family Pols; the N-terminal Pol module is catalytic and the C-terminal Pol module is non-catalytic. Despite extensive efforts, there is no atomic structure for Pol ε holoenzyme, critical to understanding how DNA synthesis is coordinated with unwinding and the DNA path through the CMG helicase-Pol ε-PCNA clamp. We show here a 3.5-Å cryo-EM structure of yeast Pol ε revealing that the Dpb3-Dpb4 subunits bridge the two DNA Pol modules of Pol2, holding them rigid. This information enabled an atomic model of the leading strand replisome. Interestingly, the model suggests that an OB fold in Dbp2 directs leading ssDNA from CMG to the Pol ε active site. These results complete the DNA path from entry of parental DNA into CMG to exit of daughter DNA from PCNA.
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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.