ArticleNucleic acids research2004
Design and synthesis of fluorescent substrates for human tyrosyl-DNA phosphodiesterase I.
Article in Nucleic acids research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors.Sensors (Basel, Switzerland) · 2021Article
- Novel group of tyrosyl-DNA-phosphodiesterase 1 inhibitors based on disaccharide nucleosides as drug prototypes for anti-cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2).DNA repair · 2014Review
- Analysis of the active-site mechanism of tyrosyl-DNA phosphodiesterase I: a member of the phospholipase D superfamily.Journal of molecular biology · 2012Article
- Effects of DNA and protein size on substrate cleavage by human tyrosyl-DNA phosphodiesterase 1.The Biochemical journal · 2011Article
- The DNA binding and 3'-end preferential activity of human tyrosyl-DNA phosphodiesterase.Nucleic acids research · 2010Article
- Identification of phosphotyrosine mimetic inhibitors of human tyrosyl-DNA phosphodiesterase I by a novel AlphaScreen high-throughput assay.Molecular cancer therapeutics · 2009Article
- Tyrosyl-DNA phosphodiesterase as a target for anticancer therapy.Anti-cancer agents in medicinal chemistry · 2008Review
- Novel high-throughput electrochemiluminescent assay for identification of human tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors and characterization of furamidine (NSC 305831) as an inhibitor of Tdp1.Nucleic acids research · 2007Article
- Repair of topoisomerase I-mediated DNA damage.Progress in nucleic acid research and molecular biology · 2006Review
- Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages.The Journal of biological chemistry · 2005Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that acts upon protein-DNA covalent complexes. Tdp1 hydrolyzes 3'-phosphotyrosyl bonds to generate 3'-phosphate DNA and free tyrosine in vitro. Mutations in Tdp1 have been linked to patients with spinocerebellar ataxia, and over-expression of Tdp1 results in resistance to known anti-cancer compounds. Tdp1 has been shown to be involved in double-strand break repair in yeast, and Tdp1 has also been implicated in single-strand break repair in mammalian cells. Despite the biological importance of this enzyme and the possibility that Tdp1 may be a molecular target for new anti-cancer drugs, there are very few assays available for screening inhibitor libraries or for characterizing Tdp1 function, especially under pre-steady-state conditions. Here, we report the design and synthesis of a fluorescence-based assay using oligonucleotide and nucleotide substrates containing 3'-(4-methylumbelliferone)-phosphate. These substrates are efficiently cleaved by Tdp1, generating the fluorescent 4-methylumbelliferone reporter molecule. The kinetic characteristics determined for Tdp1 using this assay are in agreement with the previously published values, and this fluorescence-based assay is validated using the standard gel-based methods. This sensitive assay is ideal for kinetic analysis of Tdp1 function and for high-throughput screening of Tdp1 inhibitory molecules.
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