Evidence map›Paper›PMID 24487181›Full record

ArticleJournal of molecular biology2014

Folding and unfolding pathways of the human telomeric G-quadruplex.

Robert D Gray, John O Trent, Jonathan B Chaires

Open access · hybridAbstract read
In one paragraph

Article in Journal of molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed
9.3field-weighted citation impact, top 1% 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

98 citing papers in PubMed, 199 citations in OpenAlex.

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  20. A TeZla micromixer for interrogating the early and broad folding landscape of G-quadruplex via multistage velocity descending.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Robert D GrayJames Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
John O TrentJames Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA.
Jonathan B ChairesJames Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202, USA. Electronic address: jchaires@louisville.edu.
University of Louisville · USJames Graham Brown Foundation · US

Funding

PROJ 12: STEM CELL-BASED VACCINE FOR CANCER PROPHYLAXISP20RR018733 · NCRR · UNIVERSITY OF LOUISVILLE · PI TRENT, JOHN O · 2003 to 2011
$18.9M
PILOT PROJECT PROGRAMP30GM106396 · NIGMS · UNIVERSITY OF LOUISVILLE · PI EATON, JOHN W · 2013 to 2017
$5.4M
Targeting Nucleic Acids with an Integrated Vitural and Actual ScreenR01GM077422 · NIGMS · UNIVERSITY OF LOUISVILLE · PI CHAIRES, JONATHAN B., TRENT, JOHN O · 2007 to 2020
$3.7M
SPECIFICITY OF INTERCALATION REACTIONSR01CA035635 · NCI · UNIVERSITY OF MISSISSIPPI MEDICAL CENTER · PI CHAIRES, JONATHAN B. · 1985 to 2014
$2.0M
NCI NIH HHS CA35635NCI NIH HHS R01 CA035635NCRR NIH HHS P20 RR018733NIGMS NIH HHS GM077422NIGMS NIH HHS P30 GM106396NIGMS NIH HHS R01 GM077422
6 · The paper itself

Abstract

Sequence analogs of human telomeric DNA such as d[AGGG(TTAGGG)3] (Tel22) fold into monomeric quadruplex structures in the presence of a suitable cation. To investigate the pathway for unimolecular quadruplex formation, we monitored the kinetics of K(+)-induced folding of Tel22 by circular dichroism (CD), intrinsic 2-aminopurine fluorescence, and fluorescence resonance energy transfer (FRET). The results are consistent with a four-step pathway U ↔ I1 ↔ I2 ↔ I3 ↔ F where U and F represent unfolded and folded conformational ensembles and I1, I2, and I3 are intermediates. Previous kinetic studies have shown that I1 is formed in a rapid pre-equilibrium and may consist of an ensemble of "prefolded" hairpin structures brought about by cation-induced electrostatic collapse of the DNA. The current study shows that I1 converts to I2 with a relaxation time τ1=0.1s at 25 °C in 25 mM KCl. The CD spectrum of I2 is characteristic of an antiparallel quadruplex that could form as a result of intramolecular fold-over of the I1 hairpins. I3 is relatively slowly formed (τ2≈3700s) and has CD and FRET properties consistent with those expected of a triplex structure as previously observed in equilibrium melting studies. I3 converts to F with τ3≈750s. Identical pathways with different kinetic constants involving a rapidly formed antiparallel intermediate were observed with oligonucleotides forming mixed parallel/antiparallel hybrid-1 and hybrid-2 topologies {e.g. d[TTGGG(TTAGGG)3A] and d[TAGGG(TTAGGG)3TT]}. Aspects of the kinetics of unfolding were also monitored by the spectroscopic methods listed above and by time-resolved fluorescence lifetime measurements using a complementary strand trap assay. These experiments reveal a slow, rate-limiting step along the unfolding pathway.

Indexed as

G-Quadruplexes2-AminopurineBase SequenceCircular DichroismDNADNA, Single-StrandedFluorescence Resonance Energy TransferHumansKineticsModels, MolecularMolecular Dynamics SimulationNucleic Acid ConformationPotassiumSodiumSpectrophotometry2-AminopurineDNADNA, Single-StrandedPotassiumSodiumcircular dichroismfolding intermediateskineticsstopped-flowtriplex

Identifiers

PMID24487181
PMCPMC3969789
OpenAlexW2078024052

What OpenQuestion holds

Textmetadata
LicenceTDM
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.