ArticleJournal of molecular biology2014
Insights into eukaryotic primer synthesis from structures of the p48 subunit of human DNA primase.
Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Structural and mechanistic insights into primer synthesis initiation by DNA primase.Nature communications · 2026Article
- Phylogenetic and functional characterization of Asgard primases.Molecular biology and evolution · 2026Article
- A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.Nature structural & molecular biology · 2024Article
- Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans.Genes · 2024Review
- Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism.International journal of molecular sciences · 2024Review
- Telomere C-Strand Fill-In Machinery: New Insights into the Human CST-DNA Polymerase Alpha-Primase Structures and Functions.Sub-cellular biochemistry · 2024Review
- 3'dNTP Binding Is Modulated during Primer Synthesis and Translesion by Human PrimPol.International journal of molecular sciences · 2023Article
- Flexibility and Distributive Synthesis Regulate RNA Priming and Handoff in Human DNA Polymerase α-Primase.Journal of molecular biology · 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
- Review
- Loss of heterozygosity of essential genes represents a widespread class of potential cancer vulnerabilities.Nature communications · 2020Article
- Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine.ACS chemical biology · 2019Article
- Substrate Binding Regulates Redox Signaling in Human DNA Primase.Journal of the American Chemical Society · 2018Article
- Primer synthesis by a eukaryotic-like archaeal primase is independent of its Fe-S cluster.Nature communications · 2017Article
- The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.Science (New York, N.Y.) · 2017Article
- Elaborated Action of the Human Primosome.Genes · 2017Review
- Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome.The Journal of biological chemistry · 2016Article
- Insight into the Human DNA Primase Interaction with Template-Primer.The Journal of biological chemistry · 2016Article
- Primase-polymerases are a functionally diverse superfamily of replication and repair enzymes.Nucleic acids research · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
DNA replication in all organisms requires polymerases to synthesize copies of the genome. DNA polymerases are unable to function on a bare template and require a primer. Primases are crucial RNA polymerases that perform the initial de novo synthesis, generating the first 8-10 nucleotides of the primer. Although structures of archaeal and bacterial primases have provided insights into general priming mechanisms, these proteins are not well conserved with heterodimeric (p48/p58) primases in eukaryotes. Here, we present X-ray crystal structures of the catalytic engine of a eukaryotic primase, which is contained in the p48 subunit. The structures of p48 reveal that eukaryotic primases maintain the conserved catalytic prim fold domain, but with a unique subdomain not found in the archaeal and bacterial primases. Calorimetry experiments reveal that Mn(2+) but not Mg(2+) significantly enhances the binding of nucleotide to primase, which correlates with higher catalytic efficiency in vitro. The structure of p48 with bound UTP and Mn(2+) provides insights into the mechanism of nucleotide synthesis by primase. Substitution of conserved residues involved in either metal or nucleotide binding alter nucleotide binding affinities, and yeast strains containing the corresponding Pri1p substitutions are not viable. Our results reveal that two residues (S160 and H166) in direct contact with the nucleotide were previously unrecognized as critical to the human primase active site. Comparing p48 structures to those of similar polymerases in different states of action suggests changes that would be required to attain a catalytically competent conformation capable of initiating dinucleotide synthesis.
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