ArticleNucleic acids research2019
Structural evidence for an essential Fe-S cluster in the catalytic core domain of DNA polymerase ϵ.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 45 citations in OpenAlex.
- Iron-sulfur cofactors in nucleic acid metabolism and protein synthesis: Assembly, delivery, and putative roles in cellular and viral systems.The Journal of biological chemistry · 2026Review
- A thumb-domain insertion balances processivity and fidelity in DNA polymerase ε.Nucleic acids research · 2026Article
- NFS1 Plays a Critical Role in Regulating Ferroptosis Homeostasis.Biomolecules · 2025Review
- 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
- Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery.Cells · 2025Review
- Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε.Nature structural & molecular biology · 2024Article
- Revised mechanism of hydroxyurea-induced cell cycle arrest and an improved alternative.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Structures of the human leading strand Polε-PCNA holoenzyme.Nature communications · 2024Article
- An oligopeptide permease, OppABCD, requires an iron-sulfur cluster domain for functionality.Nature structural & molecular biology · 2024Article
- A sensor complements the steric gate when DNA polymerase ϵ discriminates ribonucleotides.Nucleic acids research · 2023Article
- DNA mismatch repair protects the genome from oxygen-induced replicative mutagenesis.Nucleic acids research · 2023Article
- An iron-sulfur cluster in the zinc-binding domain of the SARS-CoV-2 helicase modulates its RNA-binding and -unwinding activities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex.Frontiers in genetics · 2023Review
- Mössbauer-based molecular-level decomposition of the Saccharomyces cerevisiae ironome, and preliminary characterization of isolated nuclei.Metallomics : integrated biometal science · 2022Article
- The iron-sulfur cluster is essential for DNA binding by human DNA polymerase ε.Scientific reports · 2022Article
- Efficient discrimination against RNA-containing primers by human DNA polymerase ε.Scientific reports · 2022Article
- Modification of the 4Fe-4S Cluster Charge Transport Pathway Alters RNA Synthesis by Yeast DNA Primase.Biochemistry · 2022Article
- Iron-sulfur clusters as inhibitors and catalysts of viral replication.Nature chemistry · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
DNA polymerase ϵ (Pol ϵ), the major leading-strand DNA polymerase in eukaryotes, has a catalytic subunit (Pol2) and three non-catalytic subunits. The N-terminal half of Pol2 (Pol2CORE) exhibits both polymerase and exonuclease activity. It has been suggested that both the non-catalytic C-terminal domain of Pol2 (with the two cysteine motifs CysA and CysB) and Pol2CORE (with the CysX cysteine motif) are likely to coordinate an Fe-S cluster. Here, we present two new crystal structures of Pol2CORE with an Fe-S cluster bound to the CysX motif, supported by an anomalous signal at that position. Furthermore we show that purified four-subunit Pol ϵ, Pol ϵ CysAMUT (C2111S/C2133S), and Pol ϵ CysBMUT (C2167S/C2181S) all have an Fe-S cluster that is not present in Pol ϵ CysXMUT (C665S/C668S). Pol ϵ CysAMUT and Pol ϵ CysBMUT behave similarly to wild-type Pol ϵ in in vitro assays, but Pol ϵ CysXMUT has severely compromised DNA polymerase activity that is not the result of an excessive exonuclease activity. Tetrad analyses show that haploid yeast strains carrying CysXMUT are inviable. In conclusion, Pol ϵ has a single Fe-S cluster bound at the base of the P-domain, and this Fe-S cluster is essential for cell viability and polymerase activity.
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