Evidence map›Paper›PMID 29741655›Full record

ArticleNucleic acids research2018

Cooperative recognition of T:T mismatch by echinomycin causes structural distortions in DNA duplex.

Pei-Ching Wu, Shu-Ling Tzeng, Chung-Ke Chang, Ya-Fen Kao, Michael J Waring, Ming-Hon Hou

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 21% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

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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

6 authors at 4 institutions in 2 countries.

Pei-Ching WuInstitute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan.
Shu-Ling TzengInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Chung-Ke ChangInstitute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Ya-Fen KaoInstitute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan.
Michael J WaringDepartment of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England.
Ming-Hon HouInstitute of Genomics and Bioinformatics, National Chung Hsing University, Taichung 40227, Taiwan.
National Chung Hsing University · TWChung Shan Medical University · TWInstitute of Biomedical Sciences, Academia Sinica · TWUniversity of Cambridge · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small-molecule compounds that target mismatched base pairs in DNA offer a novel prospective for cancer diagnosis and therapy. The potent anticancer antibiotic echinomycin functions by intercalating into DNA at CpG sites. Surprisingly, we found that the drug strongly prefers to bind to consecutive CpG steps separated by a single T:T mismatch. The preference appears to result from enhanced cooperativity associated with the binding of the second echinomycin molecule. Crystallographic studies reveal that this preference originates from the staggered quinoxaline rings of the two neighboring antibiotic molecules that surround the T:T mismatch forming continuous stacking interactions within the duplex. These and other associated changes in DNA conformation allow the formation of a minor groove pocket for tight binding of the second echinomycin molecule. We also show that echinomycin displays enhanced cytotoxicity against mismatch repair-deficient cell lines, raising the possibility of repurposing the drug for detection and treatment of mismatch repair-deficient cancers.

Indexed as

Antibiotics, AntineoplasticBase Pair MismatchCell SurvivalCrystallography, X-RayDNAEchinomycinHCT116 CellsHumansIntercalating AgentsMolecular StructureNeoplasmsNucleic Acid ConformationAntibiotics, AntineoplasticDNAEchinomycinIntercalating Agents

Identifiers

PMID29741655
PMCPMC6101601
OpenAlexW2801415647

What OpenQuestion holds

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LicenceCC BY-NC
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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.