Evidence map›Paper›PMID 22169953›Full record

ArticleNucleic acids research2012

Metal-induced DNA translocation leads to DNA polymerase conformational activation.

Thomas W Kirby, Eugene F DeRose, Nisha A Cavanaugh, William A Beard, David D Shock, Geoffrey A Mueller, Samuel H Wilson, Robert E London

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
  2. Article
  3. Structural and Molecular Kinetic Features of Activities of DNA Polymerases.International journal of molecular sciences · 2022
    Review
  4. Article
  5. Visualizing Rev1 catalyze protein-template DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Substrate-induced DNA polymerase β activation.The Journal of biological chemistry · 2014
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Structural basis for promutagenicity of 8-halogenated guanine.The Journal of biological chemistry · 2014
    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

8 authors at 2 institutions in 1 country.

Thomas W KirbyLaboratory of Structural Biology, NIEHS, Research Triangle Park, NC 27709, USA.
Eugene F DeRose
Nisha A Cavanaugh
William A Beard
David D Shock
Geoffrey A Mueller
Samuel H Wilson
Robert E London
National Institute of Environmental Health Sciences · USResearch Triangle Park Foundation · US

Funding

Epigenomics and DNA SequencingZICES102545 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WADE, PAUL A · 2012 to 2025
$27.4M
Mechanisms of Nucleic Acid Enzymes - Pol Beta, HIV-1 Reverse Transcriptase and Mammalian Base Repair EnzymesZIAES050158 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WILSON, SAMUEL H · 2009 to 2022
$17.0M
Nmr Studies Of Biomolecular Structure, Function, And DynamicsZIAES050111 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, ROBERT E · 2009 to 2020
$11.7M
Mechanistic Analysis of Pol Beta and Cancer-Associated MutantsU19CA105010 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI WARSHEL, ARIEH · 2004 to 2012
$9.8M
Aids Related Nmr ResearchZIAES050147 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI LONDON, ROBERT E · 2009 to 2020
$6.3M
Intramural NIH HHS ZIA ES050158NCI NIH HHS 1U19CA105010
6 · The paper itself

Abstract

Binding of the catalytic divalent ion to the ternary DNA polymerase β/gapped DNA/dNTP complex is thought to represent the final step in the assembly of the catalytic complex and is consequently a critical determinant of replicative fidelity. We have analyzed the effects of Mg(2+) and Zn(2+) on the conformational activation process based on NMR measurements of [methyl-(13)C]methionine DNA polymerase β. Unexpectedly, both divalent metals were able to produce a template base-dependent conformational activation of the polymerase/1-nt gapped DNA complex in the absence of a complementary incoming nucleotide, albeit with different temperature thresholds. This conformational activation is abolished by substituting Glu295 with lysine, thereby interrupting key hydrogen bonds necessary to stabilize the closed conformation. These and other results indicate that metal-binding can promote: translocation of the primer terminus base pair into the active site; expulsion of an unpaired pyrimidine, but not purine, base from the template-binding pocket; and motions of polymerase subdomains that close the active site. We also have performed pyrophosphorolysis studies that are consistent with predictions based on these results. These findings provide new insight into the relationships between conformational activation, enzyme activity and polymerase fidelity.

Indexed as

Amino Acid SubstitutionBiological TransportCations, DivalentDNADNA Polymerase betaEnzyme ActivationHot TemperatureMagnesiumNuclear Magnetic Resonance, BiomolecularProtein ConformationZincCations, DivalentDNADNA Polymerase betaMagnesiumZinc

Identifiers

PMID22169953
PMCPMC3326329
OpenAlexW2110089377

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.