Evidence map›Paper›PMID 40332112›Full record

ArticleInternational journal of molecular sciences2025

Mutagenesis of Intrinsically Disordered Domain Impacts Topoisomerase IIα Catalytic Activity.

Jeong Won Chang, Addison K O'Brian, Allison J Thomas, Mattalyn R Hardin, Brooke D Latham, Daniel Ngabonziza, Lily G Simpson, Benjamin D Wade, Laura Kühnhenrich, Nina M Thompson and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. The Roles of Topoisomerases in Transcriptional Regulation.International journal of molecular sciences · 2026
    Review
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

12 authors.

Jeong Won ChangBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Addison K O'BrianBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Allison J ThomasBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Mattalyn R HardinBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Brooke D LathamBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Daniel NgabonzizaBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Lily G SimpsonBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Benjamin D WadeBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Laura KühnhenrichBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Nina M ThompsonBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Clark E EndsleyBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.
Joseph E DeweeseBiological, Physical, and Human Sciences Department, Freed-Hardeman University, Henderson, TN 38340, USA.ORCID 0000-0001-9683-6723

Funding

Center for Science and Culture NAHeintzman Research Fund NAJobe Center for Excellence NA
6 · The paper itself

Abstract

Human topoisomerase IIα and IIβ regulate DNA topology and knots in chromosomes during crucial cellular processes, making these enzymes common targets for anticancer drugs. However, selective inhibition of topoisomerase IIα (TOP2A) is desired to decrease adverse effects, which may be mediated by topoisomerase IIβ (TOP2B). The main region of difference between the two isoforms is the intrinsically disordered C-terminal domain (CTD), which is being studied as a target for selective inhibition. Our previous work examined several regions within the CTD to determine whether those regions impact biochemical function. In this current study, we designed and constructed four TOP2A mutants with amino acid substitutions in the CTD, which were then assessed for impact on biochemical activity. V1482D exhibited increased levels of relaxation, while both V1482D and K1520I exhibited increased levels of decatenation. No major impact on DNA cleavage or binding were observed with any of the mutants. The isolated impact of the changes on relaxation and decatenation supports the concept that the CTD can affect one aspect of the enzyme's function in an isolated manner, which was seen in our previous study. Taken together, these results suggest that modification of specific positions within the CTD affects substrate selection. These results are mapped onto the CTD for consideration of potential regions to target for inhibition of TOP2A.

Indexed as

Antigens, NeoplasmDNA Topoisomerases, Type IIIntrinsically Disordered ProteinsMutagenesisPoly-ADP-Ribose Binding ProteinsAmino Acid SubstitutionDNAHumansMutationProtein DomainsAntigens, NeoplasmDNADNA Topoisomerases, Type IIIntrinsically Disordered ProteinsPoly-ADP-Ribose Binding ProteinsTOP2A protein, humancarboxy-terminal domaincleavagedecatenationDNAintrinsically disordered domainprotein disorderPSICalcrelaxationTOP2Atopoisomerase IIα

Identifiers

PMID40332112
PMCPMC12026768

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Registered trials

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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.