ArticleThe Journal of biological chemistry2012
A conserved motif in the C-terminal tail of DNA polymerase α tethers primase to the eukaryotic replisome.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Meta-analysis of loci associated with age at natural menopause in African-American women.Human molecular genetics · 2014Pooled it
- Iron-sulfur clusters in SARS-CoV-2 exoribonuclease and methyltransferase complexes: relevance for viral genome proofreading and capping.Nature communications · 2025Article
- A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.Nature structural & molecular biology · 2024Article
- Flexibility and Distributive Synthesis Regulate RNA Priming and Handoff in Human DNA Polymerase α-Primase.Journal of molecular biology · 2023Article
- How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication.Molecular cell · 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
- Selected Genetic Factors Associated with Primary Ovarian Insufficiency.International journal of molecular sciences · 2023Review
- Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex.Frontiers in genetics · 2023Review
- Structural basis for the interaction of SARS-CoV-2 virulence factor nsp1 with DNA polymerase α-primase.Protein science : a publication of the Protein Society · 2022Article
- Replication and transcription machinery for ranaviruses: components, correlation, and functional architecture.Cell & bioscience · 2022Article
- Fe-S cofactors in the SARS-CoV-2 RNA-dependent RNA polymerase are potential antiviral targets.Science (New York, N.Y.) · 2021Article
- DNA polymerase D temporarily connects primase to the CMG-like helicase before interacting with proliferating cell nuclear antigen.Nucleic acids research · 2021Article
- Structural basis for the increased processivity of D-family DNA polymerases in complex with PCNA.Nature communications · 2020Article
- Histone H2A-H2B binding by Pol α in the eukaryotic replisome contributes to the maintenance of repressive chromatin.The EMBO journal · 2018Article
- Eukaryotic DNA Replication Fork.Annual review of biochemistry · 2017Review
- The [4Fe4S] cluster of human DNA primase functions as a redox switch using DNA charge transport.Science (New York, N.Y.) · 2017Article
- Proficient Replication of the Yeast Genome by a Viral DNA Polymerase.The Journal of biological chemistry · 2016Article
- 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
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The DNA polymerase α-primase complex forms an essential part of the eukaryotic replisome. The catalytic subunits of primase and pol α synthesize composite RNA-DNA primers that initiate the leading and lagging DNA strands at replication forks. The physical basis and physiological significance of tethering primase to the eukaryotic replisome via pol α remain poorly characterized. We have identified a short conserved motif at the extreme C terminus of pol α that is critical for interaction of the yeast ortholog pol1 with primase. We show that truncation of the C-terminal residues 1452-1468 of Pol1 abrogates the interaction with the primase, as does mutation to alanine of the invariant amino acid Phe(1463). Conversely, a pol1 peptide spanning the last 16 residues binds primase with high affinity, and the equivalent peptide from human Pol α binds primase in an analogous fashion. These in vitro data are mirrored by experiments in yeast cells, as primase does not interact in cell extracts with pol1 that either terminates at residue 1452 or has the F1463A mutation. The ability to disrupt the association between primase and pol α allowed us to assess the physiological significance of primase being tethered to the eukaryotic replisome in this way. We find that the F1463A mutation in Pol1 renders yeast cells dependent on the S phase checkpoint, whereas truncation of Pol1 at amino acid 1452 blocks yeast cell proliferation. These findings indicate that tethering of primase to the replisome by pol α is critical for the normal action of DNA replication forks in eukaryotic cells.
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