Evidence map›Paper›PMID 38491139›Full record

ArticleNature structural & molecular biology2024

A mechanistic model of primer synthesis from catalytic structures of DNA polymerase α-primase.

Elwood A Mullins, Lauren E Salay, Clarissa L Durie, Noah P Bradley, Jane E Jackman, Melanie D Ohi, Walter J Chazin, Brandt F Eichman

Open access · greenAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Eukaryotic Lagging Strand Synthesis is Distributive.bioRxiv : the preprint server for biology · 2025
    Article
  5. DNA polymerase α-primase can function as a translesion DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Elwood A MullinsDepartment of Biological Sciences, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0003-3834-1065
Lauren E SalayCenter for Structural Biology, Vanderbilt University, Nashville, TN, USA.ORCID http://orcid.org/0000-0001-8513-1891
Clarissa L DurieDepartment of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
Noah P BradleyDepartment of Biological Sciences, Vanderbilt University, Nashville, TN, USA.
Jane E JackmanDepartment of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
Melanie D OhiDepartment of Cell and Developmental Biology, University of Michigan School of Medicine, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1750-4793
Walter J ChazinCenter for Structural Biology, Vanderbilt University, Nashville, TN, USA. walter.j.chazin@vanderbilt.edu.ORCID http://orcid.org/0000-0002-2180-0790
Brandt F EichmanDepartment of Biological Sciences, Vanderbilt University, Nashville, TN, USA. brandt.eichman@vanderbilt.edu.ORCID http://orcid.org/0000-0002-0965-2297
Vanderbilt University · USUniversity of Michigan · USThe Ohio State University · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI WALTER J. CHAZIN · 2001 to 2026
$89.6M
MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Structural Biology of Multi-Domain Proteins and Multi-Protein Machinery in DNA Replication and RepairR35GM118089 · NIGMS · VANDERBILT UNIVERSITY · PI WALTER J. CHAZIN · 2016 to 2026
$4.9M
The DNA replication-repair interface: mechanisms and regulationR35GM136401 · NIGMS · VANDERBILT UNIVERSITY · PI Brandt F Eichman · 2020 to 2026
$4.3M
Molecular Mechanism and Biological Function of 3'-5' PolymerasesR01GM087543 · NIGMS · OHIO STATE UNIVERSITY · PI JACKMAN, JANE ELIZABETH · 2010 to 2019
$2.7M
NCI NIH HHS P01 CA092584NIGMS NIH HHS R01 GM087543NIGMS NIH HHS R35 GM118089NIGMS NIH HHS R35 GM136401NIGMS NIH HHS T32 GM008320
6 · The paper itself

Abstract

The mechanism by which polymerase α-primase (polα-primase) synthesizes chimeric RNA-DNA primers of defined length and composition, necessary for replication fidelity and genome stability, is unknown. Here, we report cryo-EM structures of Xenopus laevis polα-primase in complex with primed templates representing various stages of DNA synthesis. Our data show how interaction of the primase regulatory subunit with the primer 5' end facilitates handoff of the primer to polα and increases polα processivity, thereby regulating both RNA and DNA composition. The structures detail how flexibility within the heterotetramer enables synthesis across two active sites and provide evidence that termination of DNA synthesis is facilitated by reduction of polα and primase affinities for the varied conformations along the chimeric primer-template duplex. Together, these findings elucidate a critical catalytic step in replication initiation and provide a comprehensive model for primer synthesis by polα-primase.

Indexed as

Cryoelectron MicroscopyDNA Polymerase IDNA PrimaseDNA ReplicationModels, MolecularXenopus laevisAnimalsCatalytic DomainDNADNA PrimersProtein ConformationRNADNADNA polymerase alpha-primaseDNA Polymerase IDNA PrimaseDNA PrimersRNARNA primers

Identifiers

PMID38491139
PMCPMC11102853
OpenAlexW4392873617

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.