ReviewNucleic acids research2018
Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.
Review in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial.Cell research · 2021Trial
- Nucleotide excision repair and poly(ADP-ribose) polymerase 1 cooperate in HBV cccDNA synthesis: A potential viral therapeutic target.JHEP reports : innovation in hepatology · 2026Article
- The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells.Current issues in molecular biology · 2026Article
- Cellular strategies for repairing trapped protein-DNA complexes.Frontiers in pharmacology · 2026Review
- Article
- Dirty Ends: Formation, Repair, and Biological Relevance of Non-Canonical DNA Terminal Structures.Genes · 2025Review
- Inhibition of DNA cleavage and strand passage activities of Mycobacterium tuberculosis topoisomerase I.Nucleic acids research · 2025Article
- Potent β-lactam-based tyrosyl-DNA phosphodiesterase 1 inhibitors identified by a virtual screen.Scientific reports · 2025Article
- Integrated analysis of hub genes and intrinsically disordered regions in triple-negative breast cancer.Journal, genetic engineering & biotechnology · 2024Article
- Insights into Nitrogen-Associated Protein 50 (NAP50) as a Tyrosyl-DNA Phosphodiesterase in Dinoflagellates.Microorganisms · 2024Article
- Cheminformatic Identification of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibitors: A Comparative Study of SMILES-Based Supervised Machine Learning Models.Journal of personalized medicine · 2024Article
- Endogenous base damage as a driver of genomic instability in homologous recombination-deficient cancers.DNA repair · 2024Review
- TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.The EMBO journal · 2024Article
- Review
- Enhancement of the Antitumor and Antimetastatic Effect of Topotecan and Normalization of Blood Counts in Mice with Lewis Carcinoma by Tdp1 Inhibitors-New Usnic Acid Derivatives.International journal of molecular sciences · 2024Article
- Enzymatic Processing of DNA-Protein Crosslinks.Genes · 2024Review
- Tyrosyl-DNA phosphodiesterase 2 (Tdp2) repairs DNA-protein crosslinks and protects against double strand breaksFrontiers in cell and developmental biology · 2024Article
- Article
- Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinksOpen biology · 2023Article
- Identification of multidentate tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors that simultaneously access the DNA, protein and catalytic-binding sites by oxime diversification.RSC chemical biology · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosyl-DNA Phosphodiesterases 1 (TDP1) and 2 (TDP2) are eukaryotic enzymes that clean-up after aberrant topoisomerase activity. While TDP1 hydrolyzes phosphotyrosyl peptides emanating from trapped topoisomerase I (Top I) from the 3' DNA ends, topoisomerase 2 (Top II)-induced 5'-phosphotyrosyl residues are processed by TDP2. Even though the canonical functions of TDP1 and TDP2 are complementary, they exhibit little structural or sequence similarity. Homozygous mutations in genes encoding these enzymes lead to the development of severe neurodegenerative conditions due to the accumulation of transcription-dependent topoisomerase cleavage complexes underscoring the biological significance of these enzymes in the repair of topoisomerase-DNA lesions in the nervous system. TDP1 can promiscuously process several blocked 3' ends generated by DNA damaging agents and nucleoside analogs in addition to hydrolyzing 3'-phosphotyrosyl residues. In addition, deficiency of these enzymes causes hypersensitivity to anti-tumor topoisomerase poisons. Thus, TDP1 and TDP2 are promising therapeutic targets and their inhibitors are expected to significantly synergize the effects of current anti-tumor therapies including topoisomerase poisons and other DNA damaging agents. This review covers the structural aspects, biology and regulation of these enzymes, along with ongoing developments in the process of discovering safe and effective TDP inhibitors.
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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.