Evidence map›Paper›PMID 38806233›Full record

ArticleNucleic acids research2024

Dynamics of the Herpes simplex virus DNA polymerase holoenzyme during DNA synthesis and proof-reading revealed by Cryo-EM.

Emil Gustavsson, Kay Grünewald, Per Elias, B Martin Hällberg

Abstract read
In one paragraph

Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Emil GustavssonDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.ORCID 0000-0003-0166-1786
Kay GrünewaldCentre for Structural Systems Biology, Deutsches Elektronen-Synchrotron DESY, Notkestraße 85, Building 15, 22607 Hamburg, Germany.
Per EliasInstitute of Biomedicine, Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Box 440, 405 30 Gothenburg, Sweden.
B Martin HällbergDepartment of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

Funding

DFG INST 152/772-1Swedish Research Council Röntgen-Ångström Cluster 2017-06702UHH
6 · The paper itself

Abstract

Herpes simplex virus 1 (HSV-1), a double-stranded DNA virus, replicates using seven essential proteins encoded by its genome. Among these, the UL30 DNA polymerase, complexed with the UL42 processivity factor, orchestrates leading and lagging strand replication of the 152 kb viral genome. UL30 polymerase is a prime target for antiviral therapy, and resistance to current drugs can arise in immunocompromised individuals. Using electron cryo-microscopy (cryo-EM), we unveil the dynamic changes of the UL30/UL42 complex with DNA in three distinct states. First, a pre-translocation state with an open fingers domain ready for nucleotide incorporation. Second, a halted elongation state where the fingers close, trapping dATP in the dNTP pocket. Third, a DNA-editing state involving significant conformational changes to allow DNA realignment for exonuclease activity. Additionally, the flexible UL30 C-terminal domain interacts with UL42, forming an extended positively charged surface binding to DNA, thereby enhancing processive synthesis. These findings highlight substantial structural shifts in the polymerase and its DNA interactions during replication, offering insights for future antiviral drug development.

Indexed as

Cryoelectron MicroscopyDNA-Directed DNA PolymeraseDNA, ViralHerpesvirus 1, HumanViral ProteinsDNA ReplicationExodeoxyribonucleasesHoloenzymesModels, MolecularProtein BindingVirus ReplicationDNA-Directed DNA PolymeraseDNA polymerase, SimplexvirusDNA, ViralExodeoxyribonucleasesHoloenzymesViral Proteins

Identifiers

PMID38806233
PMCPMC11229320

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Registered trials

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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.