Evidence map›Paper›PMID 24283923›Full record

ArticleJournal of the American Chemical Society2013

Structural insights into DNA replication without hydrogen bonds.

Karin Betz, Denis A Malyshev, Thomas Lavergne, Wolfram Welte, Kay Diederichs, Floyd E Romesberg, Andreas Marx

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Investigation of the stability of D5SIC-DNAM-incorporated DNA duplex inPhysical chemistry chemical physics : PCCP · 2024
    Article
  5. Discovery, implications and initial use of semi-synthetic organisms with an expanded genetic alphabet/code.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. The Structural Basis for Processing of Unnatural Base Pairs by DNA Polymerases.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020
    Review
  11. Article
  12. Article
  13. Snapshots of a modified nucleotide moving through the confines of a DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  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

7 authors at 2 institutions in 2 countries.

Karin BetzDepartments of Chemistry and Biology, Konstanz Research School Chemical Biology, Universität Konstanz , Universitätsstrasse 10, D-78464 Konstanz, Germany.
Denis A Malyshev
Thomas Lavergne
Wolfram Welte
Kay Diederichs
Floyd E Romesberg
Andreas Marx
University of Konstanz · DEScripps Research Institute · US

Funding

EXPANDING THE GENETIC ALPHABET BY POLYMERASE EVOLUTIONR01GM060005 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI ROMESBERG, FLOYD E. · 1999 to 2015
$4.6M
NIGMS NIH HHS GM 060005NIGMS NIH HHS R01 GM060005
6 · The paper itself

Abstract

The genetic alphabet is composed of two base pairs, and the development of a third, unnatural base pair would increase the genetic and chemical potential of DNA. d5SICS-dNaM is one of the most efficiently replicated unnatural base pairs identified to date, but its pairing is mediated by only hydrophobic and packing forces, and in free duplex DNA it forms a cross-strand intercalated structure that makes its efficient replication difficult to understand. Recent studies of the KlenTaq DNA polymerase revealed that the insertion of d5SICSTP opposite dNaM proceeds via a mutually induced-fit mechanism, where the presence of the triphosphate induces the polymerase to form the catalytically competent closed structure, which in turn induces the pairing nucleotides of the developing unnatural base pair to adopt a planar Watson-Crick-like structure. To understand the remaining steps of replication, we now report the characterization of the prechemistry complexes corresponding to the insertion of dNaMTP opposite d5SICS, as well as multiple postchemistry complexes in which the already formed unnatural base pair is positioned at the postinsertion site. Unlike with the insertion of d5SICSTP opposite dNaM, addition of dNaMTP does not fully induce the formation of the catalytically competent closed state. The data also reveal that once synthesized and translocated to the postinsertion position, the unnatural nucleobases again intercalate. Two modes of intercalation are observed, depending on the nature of the flanking nucleotides, and are each stabilized by different interactions with the polymerase, and each appear to reduce the affinity with which the next correct triphosphate binds. Thus, continued primer extension is limited by deintercalation and rearrangements with the polymerase active site that are required to populate the catalytically active, triphosphate bound conformation.

Indexed as

DNA ReplicationHydrogen BondingBase SequenceDNA PrimersModels, MolecularTaq PolymeraseDNA PrimersTaq Polymerase

Identifiers

PMID24283923
PMCPMC3982147
OpenAlexW2027011093

What OpenQuestion holds

Textmetadata
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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.