ArticleProceedings of the National Academy of Sciences of the United States of America2010
Insights into eukaryotic DNA priming from the structure and functional interactions of the 4Fe-4S cluster domain of human DNA primase.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 89 citations in OpenAlex.
- Elucidation of DNA Primase as a Drug Target in Leishmania donovani: Structure-Guided Inhibitor Identification and Biochemical Validation.Chemical biology & drug design · 2026Article
- Iron-sulfur clusters in SARS-CoV-2 exoribonuclease and methyltransferase complexes: relevance for viral genome proofreading and capping.Nature communications · 2025Article
- New Progress on DNA Primase Subunit Enzymes Research and Link to Cancer Development and Treatment Approaches.Current cancer drug targets · 2025Review
- 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
- A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.Nature structural & molecular biology · 2024Article
- Initial Primer Synthesis of a DNA Primase Monitored by Real-Time NMR Spectroscopy.Journal of the American Chemical Society · 2024Article
- Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism.International journal of molecular sciences · 2024Review
- Flexibility and Distributive Synthesis Regulate RNA Priming and Handoff in Human DNA Polymerase α-Primase.Journal of molecular biology · 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
- Flexibility and distributive synthesis regulate RNA priming and handoff in human DNA polymerase α-primase.bioRxiv : the preprint server for biology · 2023Article
- Structures of human primosome elongation complexes.Nature structural & molecular biology · 2023Article
- Mössbauer-based molecular-level decomposition of the Saccharomyces cerevisiae ironome, and preliminary characterization of isolated nuclei.Metallomics : integrated biometal science · 2022Article
- Article
- Modification of the 4Fe-4S Cluster Charge Transport Pathway Alters RNA Synthesis by Yeast DNA Primase.Biochemistry · 2022Article
- Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets.Science (New York, N.Y.) · 2021Article
- Implications of Membrane Binding by the Fe-S Cluster-Containing N-Terminal Domain in theFrontiers in genetics · 2021Article
- Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Metabolism.Frontiers in cell and developmental biology · 2021Review
- UvrC Coordinates an OJournal of the American Chemical Society · 2020Article
- SV40 T antigen interactions with ssDNA and replication protein A: a regulatory role of T antigen monomers in lagging strand DNA replication.Nucleic acids research · 2020Article
- Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
DNA replication requires priming of DNA templates by enzymes known as primases. Although DNA primase structures are available from archaea and bacteria, the mechanism of DNA priming in higher eukaryotes remains poorly understood in large part due to the absence of the structure of the unique, highly conserved C-terminal regulatory domain of the large subunit (p58C). Here, we present the structure of this domain determined to 1.7-A resolution by X-ray crystallography. The p58C structure reveals a novel arrangement of an evolutionarily conserved 4Fe-4S cluster buried deeply within the protein core and is not similar to any known protein structure. Analysis of the binding of DNA to p58C by fluorescence anisotropy measurements revealed a strong preference for ss/dsDNA junction substrates. This approach was combined with site-directed mutagenesis to confirm that the binding of DNA occurs to a distinctively basic surface on p58C. A specific interaction of p58C with the C-terminal domain of the intermediate subunit of replication protein A (RPA32C) was identified and characterized by isothermal titration calorimetry and NMR. Restraints from NMR experiments were used to drive computational docking of the two domains and generate a model of the p58C-RPA32C complex. Together, our results explain functional defects in human DNA primase mutants and provide insights into primosome loading on RPA-coated ssDNA and regulation of primase activity.
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