Evidence map›Paper›PMID 18550580›Full record

ArticleNucleic acids research2008

The modulation of topoisomerase I-mediated DNA cleavage and the induction of DNA-topoisomerase I crosslinks by crotonaldehyde-derived DNA adducts.

Thomas S Dexheimer, Albena Kozekova, Carmelo J Rizzo, Michael P Stone, Yves Pommier

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

19 citing papers in PubMed, 31 citations in OpenAlex.

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  7. Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action.International journal of environmental research and public health · 2020
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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 2 institutions in 1 country.

Thomas S DexheimerLaboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Albena Kozekova
Carmelo J Rizzo
Michael P Stone
Yves Pommier
Vanderbilt University · USNational Institutes of Health · US

Funding

Structural Biology Facility CoreP30ES000267 · NIEHS · VANDERBILT UNIVERSITY · PI GUENGERICH, F PETER · 1985 to 2014
$20.3M
DNA Topoisomerases as Target of Action of Anticancer DrugsZIABC006161 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$16.8M
SYNTHETIC APPROACHES TO PAH-ADDUCTED NUCLEOTIDESP01ES005355 · NIEHS · VANDERBILT UNIVERSITY · PI LLOYD, STEPHEN CARROLL · 1991 to 2010
$13.4M
Intramural NIH HHSNIEHS NIH HHS ES00267NIEHS NIH HHS ES05355NIEHS NIH HHS P01 ES005355NIEHS NIH HHS P30 ES000267
6 · The paper itself

Abstract

Crotonaldehyde is a representative alpha,beta-unsaturated aldehyde endowed of mutagenic and carcinogenic properties related to its propensity to react with DNA. Cyclic crotonaldehyde-derived deoxyguanosine (CrA-PdG) adducts can undergo ring opening in duplex DNA to yield a highly reactive aldehydic moiety. Here, we demonstrate that site-specifically modified DNA oligonucleotides containing a single CrA-PdG adduct can form crosslinks with topoisomerase I (Top1), both directly and indirectly. Direct covalent complex formation between the CrA-PdG adduct and Top1 is detectable after reduction with sodium cyanoborohydride, which is consistent with the formation of a Schiff base between Top1 and the ring open aldehyde form of the adduct. In addition, we show that the CrA-PdG adduct alters the cleavage and religation activities of Top1. It suppresses Top1 cleavage complexes at the adduct site and induces both reversible and irreversible cleavage complexes adjacent to the CrA-PdG adduct. The formation of stable DNA-Top1 crosslinks and the induction of Top1 cleavage complexes by CrA-PdG are mutually exclusive. Lastly, we found that crotonaldehyde induces the formation of DNA-Top1 complexes in mammalian cells, which suggests a potential relationship between formation of DNA-Top1 crosslinks and the mutagenic and carcinogenic properties of crotonaldehyde.

Indexed as

AldehydesCell LineDNA AdductsDNA Topoisomerases, Type IHumansOligodeoxyribonucleotidesStereoisomerism2-butenalAldehydesDNA AdductsDNA Topoisomerases, Type IOligodeoxyribonucleotides

Identifiers

PMID18550580
PMCPMC2475617
OpenAlexW2096766873

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.