Evidence map›Paper›PMID 29432582›Full record

ArticleNucleic acids research2018

Structural rearrangements in the mitochondrial genome of Drosophila melanogaster induced by elevated levels of the replicative DNA helicase.

Grzegorz L Ciesielski, Cristina A Nadalutti, Marcos T Oliveira, Howard T Jacobs, Jack D Griffith, Laurie S Kaguni

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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Mitochondrial DNA damage as driver of cellular outcomes.American journal of physiology. Cell physiology · 2022
    Review
  4. Review
  5. Article
  6. Article
  7. The mitochondrial R-loop.Nucleic acids research · 2019
    Article
  8. Article
  9. 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 4 institutions in 2 countries.

Grzegorz L CiesielskiDepartment of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, USA.
Cristina A NadaluttiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Marcos T OliveiraDepartment of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, USA.
Howard T JacobsInstitute of Biosciences and Medical Technology, University of Tampere, FI-33014 Tampere, Finland.
Jack D GriffithLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laurie S KaguniDepartment of Biochemistry and Molecular Biology and Center for Mitochondrial Science and Medicine, Michigan State University, East Lansing, MI, USA.
Tampere University · FIUniversity of North Carolina at Chapel Hill · USMichigan State University · USUniversity of Helsinki · FI

Funding

Vironomics and Biostatistics CoreP01CA019014 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLOSSOM A DAMANIA, NANCY JOAN RAAB-TRAUB · 1985 to 2026
$43.8M
NCI NIH HHS P01 CA019014
6 · The paper itself

Abstract

Pathological conditions impairing functions of mitochondria often lead to compensatory upregulation of the mitochondrial DNA (mtDNA) replisome machinery, and the replicative DNA helicase appears to be a key factor in regulating mtDNA copy number. Moreover, mtDNA helicase mutations have been associated with structural rearrangements of the mitochondrial genome. To evaluate the effects of elevated levels of the mtDNA helicase on the integrity and replication of the mitochondrial genome, we overexpressed the helicase in Drosophila melanogaster Schneider cells and analyzed the mtDNA by two-dimensional neutral agarose gel electrophoresis and electron microscopy. We found that elevation of mtDNA helicase levels increases the quantity of replication intermediates and alleviates pausing at the replication slow zones. Though we did not observe a concomitant alteration in mtDNA copy number, we observed deletions specific to the segment of repeated elements in the immediate vicinity of the origin of replication, and an accumulation of species characteristic of replication fork stalling. We also found elevated levels of RNA that are retained in the replication intermediates. Together, our results suggest that upregulation of mtDNA helicase promotes the process of mtDNA replication but also results in genome destabilization.

Indexed as

AnimalsCell LineDNA HelicasesDNA, MitochondrialDNA ReplicationDrosophila melanogasterDrosophila ProteinsGene DosageGenome, MitochondrialMitochondriaMitochondrial ProteinsDNA HelicasesDNA, MitochondrialDrosophila ProteinsMitochondrial Proteins

Identifiers

PMID29432582
PMCPMC5887560
OpenAlexW2792664865

What OpenQuestion holds

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LicenceCC BY-NC
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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.