ArticleThe Journal of biological chemistry2015
Crystal Structure of the Human Pol α B Subunit in Complex with the C-terminal Domain of the Catalytic Subunit.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 66 citations in OpenAlex.
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- Flexibility and Distributive Synthesis Regulate RNA Priming and Handoff in Human DNA Polymerase α-Primase.Journal of molecular biology · 2023Article
- Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.Medical oncology (Northwood, London, England) · 2023Article
- Flexibility and distributive synthesis regulate RNA priming and handoff in human DNA polymerase α-primase.bioRxiv : the preprint server for biology · 2023Article
- Unveiling the multitargeted repurposing potential of taxifolin (dihydroquercetin) in cervical cancer: an extensive MM\GBSA-based screening, and MD simulation study.Medical oncology (Northwood, London, England) · 2023Article
- Molecular choreography of primer synthesis by the eukaryotic Pol α-primase.Nature communications · 2023Article
- Molecular choreography of primer synthesis by the eukaryotic Pol α-primase.bioRxiv : the preprint server for biology · 2023Article
- Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex.Frontiers in genetics · 2023Review
- Article
- DNA polymerase epsilon binds histone H3.1-H4 and recruits MORC1 to mediate meiotic heterochromatin condensation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural and functional insight into mismatch extension by human DNA polymerase α.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- 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
- DNA polymerase D temporarily connects primase to the CMG-like helicase before interacting with proliferating cell nuclear antigen.Nucleic acids research · 2021Article
- Immune Dysfunction in Mendelian Disorders of POLA1 Deficiency.Journal of clinical immunology · 2021Review
- Biogenesis of Iron-Sulfur Clusters and Their Role in DNA Metabolism.Frontiers in cell and developmental biology · 2021Review
- Two conformations of DNA polymerase D-PCNA-DNA, an archaeal replisome complex, revealed by cryo-electron microscopy.BMC biology · 2020Article
- Structure and mechanism of B-family DNA polymerase ζ specialized for translesion DNA synthesis.Nature structural & molecular biology · 2020Article
- Structure of the processive human Pol δ holoenzyme.Nature communications · 2020Article
- Structure of the DP1-DP2 PolD complex bound with DNA and its implications for the evolutionary history of DNA and RNA polymerases.PLoS biology · 2019Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In eukaryotic DNA replication, short RNA-DNA hybrid primers synthesized by primase-DNA polymerase α (Prim-Pol α) are needed to start DNA replication by the replicative DNA polymerases, Pol δ and Pol ϵ. The C terminus of the Pol α catalytic subunit (p180C) in complex with the B subunit (p70) regulates the RNA priming and DNA polymerizing activities of Prim-Pol α. It tethers Pol α and primase, facilitating RNA primer handover from primase to Pol α. To understand these regulatory mechanisms and to reveal the details of human Pol α organization, we determined the crystal structure of p70 in complex with p180C. The structured portion of p70 includes a phosphodiesterase (PDE) domain and an oligonucleotide/oligosaccharide binding (OB) domain. The N-terminal domain and the linker connecting it to the PDE domain are disordered in the reported crystal structure. The p180C adopts an elongated asymmetric saddle shape, with a three-helix bundle in the middle and zinc-binding modules (Zn1 and Zn2) on each side. The extensive p180C-p70 interactions involve 20 hydrogen bonds and a number of hydrophobic interactions resulting in an extended buried surface of 4080 Å(2). Importantly, in the structure of the p180C-p70 complex with full-length p70, the residues from the N-terminal to the OB domain contribute to interactions with p180C. The comparative structural analysis revealed both the conserved features and the differences between the human and yeast Pol α complexes.
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