ArticleProceedings of the National Academy of Sciences of the United States of America2006
Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 157 citations in OpenAlex.
- The Influence of TDP1 Inhibitor Usnic Acid Derivative OL9-116 on the Effects of Topotecan in Human Cells.Current issues in molecular biology · 2026Article
- Validating TDP1 as an Inhibition Target for Lipophilic Nucleoside Derivative in Human Cells.International journal of molecular sciences · 2025Article
- TDP1 splice-site mutation causes HAP1 cell hypersensitivity to topoisomerase I inhibition.Nucleic acids research · 2025Article
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- 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
- Genetic control of the error-prone repair of a chromosomal double-strand break with 5' overhangs in yeast.Genetics · 2023Article
- Genetic control of the error-prone repair of a chromosomal double-strand break with 5' overhangs in yeast.bioRxiv : the preprint server for biology · 2023Article
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells.Scientific reports · 2023Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Requirements for MRN endonuclease processing of topoisomerase II-mediated DNA damage in mammalian cells.Frontiers in molecular biosciences · 2022Article
- SUMO: A Swiss Army Knife for Eukaryotic Topoisomerases.Frontiers in molecular biosciences · 2022Review
- Topoisomerase-Mediated DNA Damage in Neurological Disorders.Frontiers in aging neuroscience · 2021Review
- Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development.Science advances · 2021Article
- A conserved SUMO pathway repairs topoisomerase DNA-protein cross-links by engaging ubiquitin-mediated proteasomal degradation.Science advances · 2020Article
- Trapped topoisomerase II initiates formation of de novo duplications via the nonhomologous end-joining pathway in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Roles of SPOP in DNA Damage Response and DNA Replication.International journal of molecular sciences · 2020Review
- Debulking of topoisomerase DNA-protein crosslinks (TOP-DPC) by the proteasome, non-proteasomal and non-proteolytic pathways.DNA repair · 2020Review
- The Indenoisoquinoline LMP517: A Novel Antitumor Agent Targeting both TOP1 and TOP2.Molecular cancer therapeutics · 2020Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Agents targeting topoisomerases are active against a wide range of human tumors. Stabilization of covalent complexes, converting topoisomerases into DNA-damaging agents, is an essential aspect of cell killing by these drugs. A unique aspect of the repair of topoisomerase-mediated DNA damage is the requirement for pathways that can remove protein covalently bound to DNA. Tyrosyl-DNA phosphodiesterase (Tdp1) is an enzyme that removes phosphotyrosyl moieties bound to the 3' end of DNA. Cells lacking Tdp1 are hypersensitive to camptothecin, consistent with a role for Tdp1 in processing 3' phosphotyrosyl protein-DNA covalent complexes. Because Top2p forms a 5' phosphotyrosyl linkage with DNA, previous work predicted that Tdp1p would not be active against lesions involving Top2p. We found that deletion of the TDP1 gene in yeast confers hypersensitivity to Top2 targeting agents. Combining tdp1 mutations with deletions of genes involved in nonhomologous end joining, excision repair, or postreplication repair enhanced sensitivity to Top2 targeting drugs over the level seen with single mutants, suggesting that Tdp1 may function in collaboration with multiple pathways involved in strand break repair. tdp1 mutations can sensitize yeast cells to drugs targeting Top2 even when TOP1 is deleted. Finally, bacterially expressed yeast Tdp1p is able to remove a peptide derived from yTop2 that is covalently bound to DNA by a 5' phosphotyrosyl linkage. Our results show that Tdp1 plays more general roles in DNA repair than repair of Top1 mediated DNA damage, and may participate in repairing many types of base damage to DNA.
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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.