Evidence map›Paper›PMID 22194617›Full record

ArticleThe Journal of biological chemistry2012

Human mitochondrial DNA polymerase γ exhibits potential for bypass and mutagenesis at UV-induced cyclobutane thymine dimers.

Rajesh Kasiviswanathan, Margaret A Gustafson, William C Copeland, Joel N Meyer

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed.

  1. Article
  2. Article
  3. Rolling Circle Replication and Bypass of Damaged Nucleotides.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  4. Article
  5. Article
  6. Mitophagy and DNA damage signaling in human aging.Mechanisms of ageing and development · 2020
    Review
  7. Article
  8. Review
  9. Mitochondrial DNA replication: a PrimPol perspective.Biochemical Society transactions · 2017
    Review
  10. Article
  11. Article
  12. Mitochondrial DNA damage induced autophagy, cell death, and disease.Frontiers in bioscience (Landmark edition) · 2016
    Review
  13. Analysis of Translesion DNA Synthesis by the Mitochondrial DNA Polymerase γ.Methods in molecular biology (Clifton, N.J.) · 2016
    Article
  14. Mitochondrial DNA maintenance: an appraisal.Molecular and cellular biochemistry · 2015
    Review
  15. Review
  16. Review
  17. Mitochondria as a target of environmental toxicants.Toxicological sciences : an official journal of the Society of Toxicology · 2013
    Review
  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

4 authors.

Rajesh KasiviswanathanLaboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Margaret A Gustafson
William C Copeland
Joel N Meyer

Funding

Molecular Characterization Of The Mitochondrial Dna PolymeraseZIAES065078 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 2009 to 2025
$25.4M
Molecular Study Of The Mitochondrial DNA PolymeraseZ01ES065078 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI COPELAND, WILLIAM · 1994 to 2008
$2.8M
The Role of Mitochondrial DNA Damage in NeurodegenerationR01ES017540 · NIEHS · DUKE UNIVERSITY · PI MEYER, JOEL NEWMAN · 2011 to 2015
$1.8M
Molecular and Physiological Responses to Persistent Mitochondrial DNA DamageR21NS065468 · NINDS · DUKE UNIVERSITY · PI MEYER, JOEL NEWMAN · 2009 to 2010
$421k
Intramural NIH HHS Z01 ES065078NIEHS NIH HHS R01 ES017540NINDS NIH HHS R21 NS065468
6 · The paper itself

Abstract

Cyclobutane thymine dimers (T-T) comprise the majority of DNA damage caused by short wavelength ultraviolet radiation. These lesions generally block replicative DNA polymerases and are repaired by nucleotide excision repair or bypassed by translesion polymerases in the nucleus. Mitochondria lack nucleotide excision repair, and therefore, it is important to understand how the sole mitochondrial DNA polymerase, pol γ, interacts with irreparable lesions such as T-T. We performed in vitro DNA polymerization assays to measure the kinetics of incorporation opposite the lesion and bypass of the lesion by pol γ with a dimer-containing template. Exonuclease-deficient pol γ bypassed thymine dimers with low relative efficiency; bypass was attenuated but still detectable when using exonuclease-proficient pol γ. When bypass did occur, pol γ misincorporated a guanine residue opposite the 3'-thymine of the dimer only 4-fold less efficiently than it incorporated an adenine. Surprisingly, the pol γ exonuclease-proficient enzyme excised the incorrectly incorporated guanine at similar rates irrespective of the nature of the thymines in the template. In the presence of all four dNTPs, pol γ extended the primer after incorporation of two adenines opposite the lesion with relatively higher efficiency compared with extension past either an adenine or a guanine incorporated opposite the 3'-thymine of the T-T. Our results suggest that T-T usually stalls mitochondrial DNA replication but also suggest a mechanism for the introduction of point mutations and deletions in the mitochondrial genomes of chronically UV-exposed cells.

Indexed as

DNA RepairCyclobutanesDimerizationDNA AdductsDNA DamageDNA-Directed DNA PolymeraseDNA Polymerase gammaDNA ReplicationHumansKineticsMitochondriaMutagenesisThymineUltraviolet RaysCyclobutanesDNA AdductsDNA-Directed DNA PolymeraseDNA Polymerase gammaThymine

Identifiers

PMID22194617
PMCPMC3308766

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.