Evidence map›Paper›PMID 26013816›Full record

ArticleNucleic acids research2015

Real-time single-molecule studies of the motions of DNA polymerase fingers illuminate DNA synthesis mechanisms.

Geraint W Evans, Johannes Hohlbein, Timothy Craggs, Louise Aigrain, Achillefs N Kapanidis

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

24 citing papers in PubMed, 52 citations in OpenAlex.

  1. Article
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  6. Entropic control of the free-energy landscape of an archetypal biomolecular machine.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  7. Cooperative action of separate interaction domains promotes high-affinity DNA binding ofProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Article
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  11. Article
  12. Review
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  14. DNA replication machinery: Insights fromComputational and structural biotechnology journal · 2021
    Review
  15. Article
  16. Article
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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

5 authors at 1 institution in 1 country.

Geraint W EvansDepartment of Physics and Biological Physics Research Group, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom.
Johannes HohlbeinDepartment of Physics and Biological Physics Research Group, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom.
Timothy CraggsDepartment of Physics and Biological Physics Research Group, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom.
Louise AigrainDepartment of Physics and Biological Physics Research Group, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom.
Achillefs N KapanidisDepartment of Physics and Biological Physics Research Group, Clarendon Laboratory, University of Oxford, Parks Road, Oxford OX1 3PU, United Kingdom a.kapanidis1@physics.ox.ac.uk.
University of Oxford · GB

Funding

Biotechnology and Biological Sciences Research Council BB/H01795X/1Biotechnology and Biological Sciences Research Council BB/J00054X/1European Research Council 261227Wellcome Trust
6 · The paper itself

Abstract

DNA polymerases maintain genomic integrity by copying DNA with high fidelity. A conformational change important for fidelity is the motion of the polymerase fingers subdomain from an open to a closed conformation upon binding of a complementary nucleotide. We previously employed intra-protein single-molecule FRET on diffusing molecules to observe fingers conformations in polymerase-DNA complexes. Here, we used the same FRET ruler on surface-immobilized complexes to observe fingers-opening and closing of individual polymerase molecules in real time. Our results revealed the presence of intrinsic dynamics in the binary complex, characterized by slow fingers-closing and fast fingers-opening. When binary complexes were incubated with increasing concentrations of complementary nucleotide, the fingers-closing rate increased, strongly supporting an induced-fit model for nucleotide recognition. Meanwhile, the opening rate in ternary complexes with complementary nucleotide was 6 s(-1), much slower than either fingers closing or the rate-limiting step in the forward direction; this rate balance ensures that, after nucleotide binding and fingers-closing, nucleotide incorporation is overwhelmingly likely to occur. Our results for ternary complexes with a non-complementary dNTP confirmed the presence of a state corresponding to partially closed fingers and suggested a radically different rate balance regarding fingers transitions, which allows polymerase to achieve high fidelity.

Indexed as

DeoxyribonucleotidesDNADNA-Directed DNA PolymeraseFluorescence Resonance Energy TransferKineticsMotionProtein ConformationDeoxyribonucleotidesDNADNA-Directed DNA Polymerase

Identifiers

PMID26013816
PMCPMC4499156
OpenAlexW1643501146

What OpenQuestion holds

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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.