Evidence map›Paper›PMID 20097655›Full record

ArticleNucleic acids research2010

The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase.

Thomas S Dexheimer, Andrew G Stephen, Matthew J Fivash, Robert J Fisher, Yves Pommier

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 46 citations in OpenAlex.

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  9. Neuroprotection and repair of 3'-blocking DNA ends by glaikit (gkt) encoding Drosophila tyrosyl-DNA phosphodiesterase 1 (TDP1).Proceedings of the National Academy of Sciences of the United States of America · 2014
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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 1 institution in 1 country.

Thomas S DexheimerLaboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA.
Andrew G Stephen
Matthew J Fivash
Robert J Fisher
Yves Pommier
National Institutes of Health · US

Funding

DNA Repair, Cell Cycle Checkpoints and Apoptosis as Targets for Anticancer DrugsZIABC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$23.0M
DNA Topoisomerases as Target of Action of Anticancer DrugsZIABC006161 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 2009 to 2025
$16.8M
PROTEIN-ASSOCIATED DNA BREAKS AS INDICATOR OF TOPOISOMERASE INHIBITIONZ01BC006150 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI POMMIER, YVES · 1996 to 2008
$1.5M
Intramural NIH HHS Z01 BC006150NCI NIH HHS Z01 BC 006150-19LMPPHS HHS HHSN261200800001E
6 · The paper itself

Abstract

Human tyrosyl-DNA phosphodiesterase (Tdp1) processes 3'-blocking lesions, predominantly 3'-phosphotyrosyl bonds resulting from the trapping of topoisomerase I (Top1) cleavage complexes. The controversial ability of yeast Tdp1 to hydrolyze 5'-phosphotyrosyl linkage between topoisomerase II (Top2) and DNA raises the question whether human Tdp1 possesses 5'-end processing activity. Here we characterize the end-binding and cleavage preference of human Tdp1 using single-stranded 5'- and 3'-fluorescein-labeled oligonucleotides. We establish 3'-fluorescein as an efficient surrogate substrate for human Tdp1, provided it is attached to the DNA by a phosphodiester (but not a phosphorothioate) linkage. We demonstrate that human Tdp1 lacks the ability to hydrolyze a phosphodiester linked 5'-fluorescein. Using both fluorescence anisotropy and time-resolved fluorescence quenching techniques, we also show the preferential binding of human Tdp1 to the 3'-end. However, DNA binding competition experiments indicate that human Tdp1 binding is dependent on DNA length rather than number of DNA ends. Lastly, using surface plasmon resonance, we show that human Tdp1 selectively binds the 3'-end of DNA. Together, our results suggest human Tdp1 may act using a scanning mechanism, in which Tdp1 bind non-specifically upstream of a 3'-blocking lesion and is preferentially stabilized at 3'-DNA ends corresponding to its site of action.

Indexed as

DNADNA CleavageFluoresceinFluorescence PolarizationFluorescent DyesHumansOligonucleotidesPhosphoric Diester HydrolasesPhosphorothioate OligonucleotidesSurface Plasmon ResonanceDNAFluoresceinFluorescent DyesOligonucleotidesPhosphoric Diester HydrolasesPhosphorothioate OligonucleotidesTDP1 protein, human

Identifiers

PMID20097655
PMCPMC2853120
OpenAlexW2119090392

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.