Evidence map›Paper›PMID 35904803›Full record

ArticleNucleic acids research2022

Top3α is the replicative topoisomerase in mitochondrial DNA replication.

Anu Hangas, Nina J Kekäläinen, Alisa Potter, Craig Michell, Kauko J Aho, Chiara Rutanen, Johannes N Spelbrink, Jaakko L Pohjoismäki, Steffi Goffart

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 25 citations in OpenAlex.

  1. The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026
    Review
  2. Differential roles of type I topoisomerases in regulating HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Identification of aFrontiers in pharmacology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Mitochondrial DNA depletion syndrome and its cardiac complication.Frontiers in cardiovascular medicine · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
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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

9 authors at 2 institutions in 2 countries.

Anu HangasDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Nina J KekäläinenDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Alisa PotterDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Craig MichellDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Kauko J AhoDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Chiara RutanenDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Johannes N SpelbrinkRadboud Center for Mitochondrial Medicine, Department of Paediatrics, Radboudumc, Nijmegen, The Netherlands.ORCID 0000-0002-9756-2602
Jaakko L PohjoismäkiDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.
Steffi GoffartDepartment of Environmental and Biological Sciences, University of Eastern Finland, PO Box 111, 80101 Joensuu, Finland.ORCID 0000-0001-8491-1458
University of Eastern Finland · FIRadboud University Nijmegen · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitochondrial DNA has been investigated for nearly fifty years, but many aspects of the maintenance of this essential small genome remain unknown. Like any genome, mammalian mitochondrial DNA requires the function of topoisomerases to counter and regulate the topological tension arising during replication, transcription, segregation, and repair. However, the functions of the different mitochondrial topoisomerases are poorly understood. Here, we investigate the role of Topoisomerase 3α (Top3α) in mtDNA replication and transcription, providing evidence that this enzyme, previously reported to act in mtDNA segregation, also participates in mtDNA replication fork progression. Top3α knockdown caused replication fork stalling, increased mtDNA catenation and decreased mtDNA levels. Overexpression in contrast induced abundant double-strand breaks around the replication origin OH and abortion of early replication, while at the same time improving the resolution of mtDNA replication termination intermediates. Both Top3α knockdown and overexpression affected mitochondrial RNA transcription, leading to a decrease in steady-state levels of mitochondrial transcripts. Together, our results indicate that the mitochondrial isoform of Top3α is not only involved in mtDNA segregation, as reported previously, but also supports the progression of the replication fork. Mitochondrial Top3α is also influencing the progression of transcription, with its absence affecting downstream transcript levels.

Indexed as

DNA ReplicationDNA Topoisomerases, Type IAnimalsDNA, MitochondrialMammalsMitochondriaReplication OriginDNA, MitochondrialDNA Topoisomerases, Type I

Identifiers

PMID35904803
PMCPMC9410902
OpenAlexW4288711838

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.