Evidence map›Paper›PMID 28449123›Full record

ArticleNucleic acids research2017

Capturing a mammalian DNA polymerase extending from an oxidized nucleotide.

Amy M Whitaker, Mallory R Smith, Matthew A Schaich, Bret D Freudenthal

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2017. 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
1.6field-weighted citation impact, top 17% 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, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Structural and Molecular Kinetic Features of Activities of DNA Polymerases.International journal of molecular sciences · 2022
    Review
  5. Article
  6. Interlocking activities of DNA polymerase β in the base excision repair pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  7. The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair.International journal of molecular sciences · 2022
    Review
  8. Article
  9. Article
  10. Article
  11. Visualizing Rev1 catalyze protein-template DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  12. Article
  13. Article
  14. Structure and function relationships in mammalian DNA polymerases.Cellular and molecular life sciences : CMLS · 2020
    Review
  15. Article
  16. Catalytic mechanism of DNA polymerases-Two metal ions or three?Protein science : a publication of the Protein Society · 2019
    Review
  17. Review
  18. Apurinic/apyrimidinic (AP) endonuclease 1 processing of AP sites with 5' mismatches.Acta crystallographica. Section D, Structural biology · 2018
    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

4 authors at 1 institution in 1 country.

Amy M WhitakerDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Mallory R SmithDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Matthew A SchaichDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Bret D FreudenthalDepartment of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
University of Kansas Medical Center · US

Funding

DNA Repair Strategies that Impact Genomic Stability During Oxidative StressR00ES024431 · NIEHS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI FREUDENTHAL, BRET D · 2015 to 2017
$734k
NIEHS NIH HHS R00 ES024431
6 · The paper itself

Abstract

The oxidized nucleotide, 8-oxo-7,8-dihydro-2΄-deoxyguanosine (8-oxoG), is one of the most abundant DNA lesions. 8-oxoG plays a major role in tumorigenesis and human disease. Biological consequences of 8-oxoG are mediated in part by its insertion into the genome, making it essential to understand how DNA polymerases handle 8-oxoG. Insertion of 8-oxoG is mutagenic when opposite adenine but not when opposite cytosine. However, either result leads to DNA damage at the primer terminus (3΄-end) during the succeeding insertion event. Extension from DNA damage at primer termini remains poorly understood. Using kinetics and time-lapse crystallography, we evaluated how a model DNA polymerase, human polymerase β, accommodates 8-oxoG at the primer terminus opposite cytosine and adenine. Notably, extension from the mutagenic base pair is favored over the non-mutagenic base pair. When 8-oxoG is at the primer terminus opposite cytosine, DNA centric changes lead to a clash between O8 of 8-oxoG and the phosphate backbone. Changes in the extension reaction resulting from the altered active site provide evidence for a stabilizing interaction between Arg254 and Asp256 that serves an important role during DNA synthesis reactions. These results provide novel insights into the impact of damage at the primer terminus on genomic stability and DNA synthesis.

Indexed as

8-Hydroxy-2'-DeoxyguanosineBiocatalysisCalciumCatalytic DomainCrystallography, X-RayDeoxyguanosineDNA Polymerase betaHumansKineticsModels, MolecularOxidation-ReductionPolymerizationProtein BindingProtein Conformation, alpha-Helical8-Hydroxy-2'-DeoxyguanosineCalciumDeoxyguanosineDNA Polymerase beta

Identifiers

PMID28449123
PMCPMC5499815
OpenAlexW2609765635

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.