Evidence map›Paper›PMID 25280269›Full record

ArticleBiochemistry2014

Catalytic core of human topoisomerase IIα: insights into enzyme-DNA interactions and drug mechanism.

R Hunter Lindsey, MaryJean Pendleton, Rachel E Ashley, Susan L Mercer, Joseph E Deweese, Neil Osheroff

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 31 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 2 institutions in 1 country.

R Hunter LindseyDepartment of Biochemistry, ‡Department of Pharmacology, and §Department of Medicine (Hematology/Oncology), Vanderbilt University School of Medicine , Nashville, Tennessee 37232-0146, United States.
MaryJean Pendleton
Rachel E Ashley
Susan L Mercer
Joseph E Deweese
Neil Osheroff
Lipscomb University · USVA Tennessee Valley Healthcare System · US

Funding

MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
BIOCHEMICAL &CHEMICAL TRAINING FOR CANCER RESEARCHT32CA009582 · NCI · VANDERBILT UNIVERSITY · PI David K Cortez · 1987 to 2026
$8.8M
FUNCTION AND BIOLOGY OF EUKARYOTIC DNA TOPOISOMERASESR01GM033944 · NIGMS · VANDERBILT UNIVERSITY · PI OSHEROFF, NEIL · 1985 to 2015
$5.5M
NCI NIH HHS T32 CA009582NCI NIH HHS T32 CA009592NCI NIH HHS T32 CA09582NIGMS NIH HHS GM033944NIGMS NIH HHS R01 GM033944
6 · The paper itself

Abstract

Coordination between the N-terminal gate and the catalytic core of topoisomerase II allows the proper capture, cleavage, and transport of DNA during the catalytic cycle. Because the activities of these domains are tightly linked, it has been difficult to discern their individual contributions to enzyme-DNA interactions and drug mechanism. To further address the roles of these domains, we analyzed the activity of the catalytic core of human topoisomerase IIα. The catalytic core and the wild-type enzyme both maintained higher levels of cleavage with negatively (as compared to positively) supercoiled plasmid, indicating that the ability to distinguish supercoil handedness is embedded within the catalytic core. However, the catalytic core alone displayed little ability to cleave DNA substrates that did not intrinsically provide the enzyme with a transport segment (i.e., substrates that did not contain crossovers). Finally, in contrast to interfacial topoisomerase II poisons, covalent poisons did not enhance DNA cleavage mediated by the catalytic core. This distinction allowed us to further characterize the mechanism of etoposide quinone, a drug metabolite that functions primarily as a covalent poison. Etoposide quinone retained some ability to enhance DNA cleavage mediated by the catalytic core, indicating that it still can function as an interfacial poison. These results further define the distinct contributions of the N-terminal gate and the catalytic core to topoisomerase II function. The catalytic core senses the handedness of DNA supercoils during cleavage, while the N-terminal gate is critical for capturing the transport segment and for the activity of covalent poisons.

Indexed as

Models, MolecularAntigens, NeoplasmBenzoquinonesBinding SitesBiocatalysisCatalytic DomainDNA-Binding ProteinsDNA, CircularDNA CleavageDNA, SuperhelicalDNA Topoisomerases, Type IIEtoposideHumansKineticsMolecular ConformationPeptide FragmentsAntigens, NeoplasmBenzoquinonesDNA-Binding ProteinsDNA, CircularDNA, SuperhelicalDNA Topoisomerases, Type IIEtoposidePeptide FragmentsquinoneRecombinant Fusion ProteinsthymoquinoneTopoisomerase II Inhibitors

Identifiers

PMID25280269
PMCPMC4204876
OpenAlexW2330207472

What OpenQuestion holds

Textmetadata
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.