ArticleThe Journal of biological chemistry2005
Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.
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Who cites it
129 citing papers in PubMed, 218 citations in OpenAlex.
- 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
- Targeting DNA Topoisomerase I for the Treatment of Cancer: Past, Present and Future.Journal of molecular biology · 2026Review
- H263A and SCAN1/H493R mutant TDP1 block TOP1-induced double-strand break repair during gene transcription in quiescent cells and promote cell death.Cell death & disease · 2025Article
- Role of TDP2 in the repair of DNA damage induced by the radiomimetic drug Bleomycin.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Untargeted Mutation Triggered by Ribonucleoside Embedded in DNA.International journal of molecular sciences · 2024Article
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- PARP1-dependent DNA-protein crosslink repair.Nature communications · 2024Article
- Homologous recombination contributes to the repair of acetaldehyde-induced DNA damage.Cell cycle (Georgetown, Tex.) · 2024Article
- Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinksOpen biology · 2023Article
- Genetic control of the error-prone repair of a chromosomal double-strand break with 5' overhangs in yeast.Genetics · 2023Article
- Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex.Nature communications · 2023Article
- MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links.BMC biology · 2023Article
- Article
- 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
- N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells.Scientific reports · 2023Article
- 4-Methylumbelliferone Targets Revealed by Public Data Analysis and Liver Transcriptome Sequencing.International journal of molecular sciences · 2023Article
- CDK7 Inhibition Synergizes with Topoisomerase I Inhibition in Small Cell Lung Cancer Cells by Inducing Ubiquitin-Mediated Proteolysis of RNA Polymerase II.Molecular cancer therapeutics · 2022Article
- Article
- Synthesis of 11-aminoalkoxy substituted benzophenanthridine derivatives as tyrosyl-DNA phosphodiesterase 1 inhibitors and their anticancer activity.Bioorganic chemistry · 2022Article
69 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Human tyrosyl-DNA phosphodiesterase (Tdp1) hydrolyzes the phosphodiester bond between a DNA 3' end and a tyrosyl moiety. In eukaryotic cells, this type of linkage is found in stalled topoisomerase I-DNA covalent complexes, and Tdp1 has been implicated in the repair of such complexes in vivo. We confirm here that the Tdp1 catalytic cycle involves a covalent reaction intermediate in which a histidine residue is connected to a DNA 3'-phosphate through a phosphoamide linkage. Most surprisingly, this linkage can be hydrolyzed by Tdp1, and unlike a topoisomerase I-DNA complex, which requires modification to be an efficient substrate for Tdp1, the native form of Tdp1 can be removed from the DNA. The spinocerebellar ataxia with axonal neuropathy neurodegenerative disease is caused by the H493R mutant form of Tdp1, which shows reduced enzymatic activity and accumulates the Tdp1-DNA covalent intermediate. The ability of wild type Tdp1 to remove the stalled mutant protein from the DNA likely explains the recessive nature of spinocerebellar ataxia with axonal neuropathy. In addition to its activity on phosphotyrosine and phosphohistidine substrates, Tdp1 also possesses a limited DNA and RNA 3'-exonuclease activity in which a single nucleoside is removed from the 3'-hydroxyl end of the substrate. Furthermore, Tdp1 also removes a 3' abasic site and an artificial 3'-biotin adduct from the DNA. In combination with earlier data showing that Tdp1 can use 3'-phosphoglycolate as a substrate, these data suggest that Tdp1 may function to remove a variety of 3' adducts from DNA during DNA repair.
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