Evidence map›Paper›PMID 30239839›Full record

ArticleNucleic acids research2018

Transcript availability dictates the balance between strand-asynchronous and strand-coupled mitochondrial DNA replication.

Tricia J Cluett, Gokhan Akman, Aurelio Reyes, Lawrence Kazak, Alice Mitchell, Stuart R Wood, Antonella Spinazzola, Johannes N Spelbrink, Ian J Holt

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

19 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Safeguarding DNA Replication: A Golden Touch of MiDAS and Other Mechanisms.International journal of molecular sciences · 2022
    Review
  10. Article
  11. R-Loops and Mitochondrial DNA Metabolism.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. The mitochondrial R-loop.Nucleic acids research · 2019
    Article
  19. 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

9 authors at 5 institutions in 3 countries.

Tricia J CluettMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB1 9SY, UK.
Gokhan AkmanMRC Mill Hill Laboratory, Mill Hill, London, UK.
Aurelio ReyesMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB1 9SY, UK.
Lawrence KazakMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB1 9SY, UK.
Alice MitchellDepartment of Clinical Movement Neurosciences, Institute of Neurology, Royal Free Campus, University College London, London NW3 2PF, UK.
Stuart R WoodMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB1 9SY, UK.
Antonella SpinazzolaDepartment of Clinical Movement Neurosciences, Institute of Neurology, Royal Free Campus, University College London, London NW3 2PF, UK.
Johannes N SpelbrinkDepartment of Pediatrics, Radboud Centre for Mitochondrial Medicine, Radboud University Medical Centre, Geert Grooteplein 10, 6500 HB, Nijmegen, The Netherlands.
Ian J HoltDepartment of Clinical Movement Neurosciences, Institute of Neurology, Royal Free Campus, University College London, London NW3 2PF, UK.
University of Cambridge · GBThe Royal Free Hospital · GBIkerbasque · ESKings Mill Hospital · GBRadboud University Nijmegen · NL

Funding

Medical Research Council MC_PC_13029Medical Research Council MC_PC_13029/2Medical Research Council MC_U105663140
6 · The paper itself

Abstract

Mammalian mitochondria operate multiple mechanisms of DNA replication. In many cells and tissues a strand-asynchronous mechanism predominates over coupled leading and lagging-strand DNA synthesis. However, little is known of the factors that control or influence the different mechanisms of replication, and the idea that strand-asynchronous replication entails transient incorporation of transcripts (aka bootlaces) is controversial. A firm prediction of the bootlace model is that it depends on mitochondrial transcripts. Here, we show that elevated expression of Twinkle DNA helicase in human mitochondria induces bidirectional, coupled leading and lagging-strand DNA synthesis, at the expense of strand-asynchronous replication; and this switch is accompanied by decreases in the steady-state level of some mitochondrial transcripts. However, in the so-called minor arc of mitochondrial DNA where transcript levels remain high, the strand-asynchronous replication mechanism is instated. Hence, replication switches to a strand-coupled mechanism only where transcripts are scarce, thereby establishing a direct correlation between transcript availability and the mechanism of replication. Thus, these findings support a critical role of mitochondrial transcripts in the strand-asynchronous mechanism of mitochondrial DNA replication; and, as a corollary, mitochondrial RNA availability and RNA/DNA hybrid formation offer means of regulating the mechanisms of DNA replication in the organelle.

Indexed as

AnimalsBase PairingDNA HelicasesDNA, MitochondrialDNA ReplicationDNA, Single-StrandedGene Expression RegulationGenomic InstabilityHEK293 CellsHumansMammalsMitochondrial ProteinsMutagenesis, Site-DirectedMutant ProteinsNucleic Acid ConformationRNA, MitochondrialDNA HelicasesDNA, MitochondrialDNA, Single-StrandedMitochondrial ProteinsMutant ProteinsRNA, MitochondrialTWNK protein, human

Identifiers

PMID30239839
PMCPMC6237803
OpenAlexW2889592648

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.