Evidence map›Paper›PMID 29712893›Full record

ArticleNature communications2018

Linear mitochondrial DNA is rapidly degraded by components of the replication machinery.

Viktoriya Peeva, Daniel Blei, Genevieve Trombly, Sarah Corsi, Maciej J Szukszto, Pedro Rebelo-Guiomar, Payam A Gammage, Alexei P Kudin, Christian Becker, Janine Altmüller and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.

0numbers the graph read from it
0cells of the map it votes in
140citing papers in PubMed
7.9field-weighted citation impact, top 2% 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

140 citing papers in PubMed, 212 citations in OpenAlex.

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80 more citing papers are in PubMed but not listed here.

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

13 authors at 4 institutions in 3 countries.

Viktoriya PeevaInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Daniel BleiInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Genevieve TromblyInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Sarah CorsiInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Maciej J SzuksztoMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK.
Pedro Rebelo-GuiomarMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK.
Payam A GammageMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK.
Alexei P KudinInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany.
Christian BeckerCologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, Cologne, D-50931, Germany.
Janine AltmüllerCologne Center for Genomics, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Weyertal 115b, Cologne, D-50931, Germany.
Michal MinczukMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, CB2 0XY, UK. michal.minczuk@mrc-mbu.cam.ac.uk.ORCID http://orcid.org/0000-0001-8242-1420
Gábor ZsurkaInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany. gabor.zsurka@ukbonn.de.ORCID http://orcid.org/0000-0002-6379-849X
Wolfram S KunzInstitute of Experimental Epileptology and Cognition Research, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany. wolfram.kunz@ukbonn.de.ORCID http://orcid.org/0000-0003-1113-3493
University of Bonn · DEUniversity of Cambridge · GBUniversity of Cologne · DEUniversidade do Porto · PT

Funding

Medical Research Council MC_U105697135Medical Research Council MC_UU_00015/4
6 · The paper itself

Abstract

Emerging gene therapy approaches that aim to eliminate pathogenic mutations of mitochondrial DNA (mtDNA) rely on efficient degradation of linearized mtDNA, but the enzymatic machinery performing this task is presently unknown. Here, we show that, in cellular models of restriction endonuclease-induced mtDNA double-strand breaks, linear mtDNA is eliminated within hours by exonucleolytic activities. Inactivation of the mitochondrial 5'-3'exonuclease MGME1, elimination of the 3'-5'exonuclease activity of the mitochondrial DNA polymerase POLG by introducing the p.D274A mutation, or knockdown of the mitochondrial DNA helicase TWNK leads to severe impediment of mtDNA degradation. We do not observe similar effects when inactivating other known mitochondrial nucleases (EXOG, APEX2, ENDOG, FEN1, DNA2, MRE11, or RBBP8). Our data suggest that rapid degradation of linearized mtDNA is performed by the same machinery that is responsible for mtDNA replication, thus proposing novel roles for the participating enzymes POLG, TWNK, and MGME1.

Indexed as

DNA CleavageDNA ReplicationBase SequenceCRISPR-Cas SystemsDeoxyribonucleases, Type II Site-SpecificDNA Breaks, Double-StrandedDNA HelicasesDNA, MitochondrialDNA Polymerase gammaElectron Transport Complex IVExodeoxyribonucleasesGene EditingGenetic TherapyHEK293 CellsHumansMitochondriaCOX8C protein, humanCTGCAG-specific type II deoxyribonucleasesDeoxyribonucleases, Type II Site-SpecificDNA HelicasesDNA, MitochondrialDNA Polymerase gammaElectron Transport Complex IVendodeoxyribonuclease XmaIIIExodeoxyribonucleasesMGME1 protein, humanPOLG protein, humanRecombinant Fusion Proteins

Identifiers

PMID29712893
PMCPMC5928156
OpenAlexW2806941167

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.