Evidence map›Paper›PMID 27364318›Full record

ArticleScientific reports2016

Oxidative DNA damage stalls the human mitochondrial replisome.

Gorazd Stojkovič, Alena V Makarova, Paulina H Wanrooij, Josefin Forslund, Peter M Burgers, Sjoerd Wanrooij

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 69 citations in OpenAlex.

  1. Article
  2. Article
  3. Mouse PrimPol Outperforms Its Human Counterpart as a Robust DNA Primase.International journal of molecular sciences · 2025
    Article
  4. Accurate DNA Synthesis Across 8-Oxoadenine by Human PrimPol.International journal of molecular sciences · 2025
    Article
  5. Article
  6. Mitochondria-Nuclear Crosstalk: Orchestrating mtDNA Maintenance.Environmental and molecular mutagenesis · 2025
    Review
  7. Article
  8. Article
  9. Rolling Circle Replication and Bypass of Damaged Nucleotides.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

6 authors at 2 institutions in 3 countries.

Gorazd StojkovičDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Alena V MakarovaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Paulina H WanrooijDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Josefin ForslundDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Peter M BurgersDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Sjoerd WanrooijDepartment of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
Umeå University · SEWashington University in St. Louis · US

Funding

MECHANISMS OF DNA REPLICATION AND MAINTENANCE IN EUKARYOTESR35GM118129 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 2016 to 2025
$6.7M
ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNAR01GM032431 · NIGMS · WASHINGTON UNIVERSITY · PI BURGERS, PETER M · 1985 to 2015
$6.5M
NIGMS NIH HHS R01 GM032431NIGMS NIH HHS R35 GM118129
6 · The paper itself

Abstract

Oxidative stress is capable of causing damage to various cellular constituents, including DNA. There is however limited knowledge on how oxidative stress influences mitochondrial DNA and its replication. Here, we have used purified mtDNA replication proteins, i.e. DNA polymerase γ holoenzyme, the mitochondrial single-stranded DNA binding protein mtSSB, the replicative helicase Twinkle and the proposed mitochondrial translesion synthesis polymerase PrimPol to study lesion bypass synthesis on oxidative damage-containing DNA templates. Our studies were carried out at dNTP levels representative of those prevailing either in cycling or in non-dividing cells. At dNTP concentrations that mimic those in cycling cells, the replication machinery showed substantial stalling at sites of damage, and these problems were further exacerbated at the lower dNTP concentrations present in resting cells. PrimPol, the translesion synthesis polymerase identified inside mammalian mitochondria, did not promote mtDNA replication fork bypass of the damage. This argues against a conventional role for PrimPol as a mitochondrial translesion synthesis DNA polymerase for oxidative DNA damage; however, we show that Twinkle, the mtDNA replicative helicase, is able to stimulate PrimPol DNA synthesis in vitro, suggestive of an as yet unidentified role of PrimPol in mtDNA metabolism.

Indexed as

DNA DamageDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA HelicasesDNA, MitochondrialDNA Polymerase gammaDNA PrimaseDNA ReplicationHumansMitochondriaMitochondrial ProteinsMultifunctional EnzymesOxidative StressDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA HelicasesDNA, MitochondrialDNA Polymerase gammaDNA PrimaseMitochondrial ProteinsMultifunctional EnzymesNABP2 protein, humanPrimPol protein, humanTWNK protein, human

Identifiers

PMID27364318
PMCPMC4929447
OpenAlexW2469625055

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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.