Evidence map›Paper›PMID 16114891›Full record

ArticleBiochemistry2005

Impact of the C-terminal domain of topoisomerase IIalpha on the DNA cleavage activity of the human enzyme.

Jennifer S Dickey, Neil Osheroff

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

34 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Mitotic chromosomes.Seminars in cell & developmental biology · 2021
    Review
  7. Article
  8. Review
  9. Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution.Cellular and molecular life sciences : CMLS · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The Roles of DNA Topoisomerase IIβ in Transcription.International journal of molecular sciences · 2018
    Review
  16. Article
  17. Non-Catalytic Roles of the Topoisomerase IIα C-Terminal Domain.International journal of molecular sciences · 2017
    Review
  18. Article
  19. Article
  20. Article
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

2 authors at 1 institution in 1 country.

Jennifer S DickeyDepartment of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.
Neil Osheroff
Vanderbilt University · US

Funding

FUNCTION AND BIOLOGY OF EUKARYOTIC DNA TOPOISOMERASESR01GM033944 · NIGMS · VANDERBILT UNIVERSITY · PI OSHEROFF, NEIL · 1985 to 2015
$5.5M
Reproductive Biology: Training for the 21st CenturyT32HD007043 · NICHD · VANDERBILT UNIVERSITY · PI OSTEEN, KEVIN G · 1985 to 2011
$2.3M
NICHD NIH HHS 5 T32 HD07043NICHD NIH HHS T32 HD007043NIGMS NIH HHS GM33944NIGMS NIH HHS R01 GM033944
6 · The paper itself

Abstract

The enzymatic function of the C-terminal domain of eukaryotic topoisomerase II is not well defined. This region of the enzyme is highly variable and hydrophilic and contains nuclear localization signals and phosphorylation sites. In contrast to eukaryotic topoisomerase II, type II enzymes from chlorella virus completely lack the C-terminal domain. These viral enzymes are characterized by a robust DNA cleavage activity, high coordination between their two active site tyrosyl residues, and reduced sensitivity to anticancer drugs. As a first step toward characterizing the contribution of the C-terminal domain of human topoisomerase IIalpha to enzyme function, the protein was truncated at amino acid 1175, which corresponds to the C-terminal residue of Paramecium bursaria chlorella virus-1 topoisomerase II as determined by BLAST sequence alignment. Although the overall catalytic activity of the resulting enzyme, hTop2alphaDelta1175, was lower than that of full-length topoisomerase IIalpha, the mutant protein displayed a double-stranded DNA cleavage activity that was approximately 2-3-fold higher. While the DNA breaks created by hTop2alphaDelta1175 were primarily double stranded, cuts generated by topoisomerase IIalpha were primarily single stranded. Thus, the enhanced cleavage observed for hTop2alphaDelta1175 appears to be due, at least in part, to an increase in active site coordination. Finally, hTop2alphaDelta1175 displayed a distinctly lower susceptibility to anticancer agents than did topoisomerase IIalpha, despite the fact that it showed a similar binding affinity for etoposide. Therefore, the C-terminal domain of human topoisomerase IIalpha appears to play significant roles in modulating the DNA cleavage/ligation reaction of the enzyme and its response to anticancer agents.

Indexed as

AnimalsAntigens, NeoplasmBinding SitesCrithidia fasciculataDNADNA-Binding ProteinsDNA Topoisomerases, Type IIEtoposideHumansKineticsPeptide FragmentsPlasmidsAntigens, NeoplasmDNADNA-Binding ProteinsDNA Topoisomerases, Type IIEtoposidePeptide Fragments

Identifiers

PMID16114891
PMCPMC2678941
OpenAlexW2050407942

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.