Evidence map›Paper›PMID 33454015›Full record

ArticleThe Journal of biological chemistry2020

Polymerase γ efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex.

Eric D Sullivan, Matthew J Longley, William C Copeland

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.0field-weighted citation impact, top 25% 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

15 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. TheGenes · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. G-quadruplex propensity inNAR genomics and bioinformatics · 2024
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
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

3 authors at 1 institution in 1 country.

Eric D SullivanMitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Matthew J LongleyMitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, USA.
William C CopelandMitochondrial DNA Replication Group, Genome Integrity and Structural Biology Laboratory, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina, USA. Electronic address: copelan1@niehs.nih.gov.
National Institutes of Health · US

Funding

Molecular Study Of The Mitochondrial DNA PolymeraseZ01ES065078 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 1994 to 2008
$2.8M
Intramural NIH HHS Z01 ES065078
6 · The paper itself

Abstract

Faithful replication of the mitochondrial genome is carried out by a set of key nuclear-encoded proteins. DNA polymerase γ is a core component of the mtDNA replisome and the only replicative DNA polymerase localized to mitochondria. The asynchronous mechanism of mtDNA replication predicts that the replication machinery encounters dsDNA and unique physical barriers such as structured genes, G-quadruplexes, and other obstacles. In vitro experiments here provide evidence that the polymerase γ heterotrimer is well-adapted to efficiently synthesize DNA, despite the presence of many naturally occurring roadblocks. However, we identified a specific G-quadruplex-forming sequence at the heavy-strand promoter (HSP1) that has the potential to cause significant stalling of mtDNA replication. Furthermore, this structured region of DNA corresponds to the break site for a large (3,895 bp) deletion observed in mitochondrial disease patients. The presence of this deletion in humans correlates with UV exposure, and we have found that efficiency of polymerase γ DNA synthesis is reduced after this quadruplex is exposed to UV in vitro.

Indexed as

G-QuadruplexesBiocatalysisDNA, MitochondrialDNA Polymerase gammaDNA ReplicationHumansMitochondriaMitochondrial DiseasesPromoter Regions, GeneticSubstrate SpecificityUltraviolet RaysDNA, MitochondrialDNA Polymerase gammaDNA polymerase γDNA replicationDNA structureG-quadruplexheavy-strand promotermitochondrial DNA damagemitochondrial DNA (mtDNA)mtDNA deletion

Identifiers

PMID33454015
PMCPMC7762954
OpenAlexW3093259099

What OpenQuestion holds

Textmetadata
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.