Affinage

TDP1

Tyrosyl-DNA phosphodiesterase 1 · UniProt Q9NUW8

Length
608 aa
Mass
68.4 kDa
Annotated
2026-06-10
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TDP1 is a phosphodiesterase of the phospholipase D superfamily that resolves a broad spectrum of 3'-blocking DNA-end adducts to enable single- and double-strand break repair in both the nucleus and mitochondria (PMID:11572945, PMID:22375014, PMID:21041670). It hydrolyzes 3'-phosphotyrosyl linkages of trapped topoisomerase I cleavage complexes and also processes 3'-phosphoglycolates, 3'-deoxyribose phosphates, chain-terminating nucleoside analogs, abasic-site-derived 3'-PUA-protein crosslinks, and 5'-phosphotyrosyl topoisomerase II adducts (PMID:22375014, PMID:15647511, PMID:23775789, PMID:35349719, PMID:16751265). Catalysis proceeds by a two-step mechanism in which His263 acts as the nucleophile to form a covalent phosphohistidine-DNA intermediate, as established by active-site mutagenesis and transition-state-mimic crystal structures, with bulky protein adducts requiring proteolytic trimming before TDP1 can act (PMID:11572945, PMID:12470949, PMID:12618186). TDP1 is recruited to break sites within the XRCC1/DNA ligase IIIα single-strand break repair machinery and through direct interactions with PARP1 (which PARylates it) and the NHEJ factor XLF, and it contributes to NHEJ fidelity and suppression of TOP1-induced chromosomal translocations (PMID:13679147, PMID:17600775, PMID:24493735, PMID:25841101, PMID:29078113, PMID:37945566). Its abundance, recruitment, and activity are tuned post-translationally: ATM/DNA-PK phosphorylation at S81 stabilizes the protein and promotes XRCC1/Lig3α and XLF complex formation, SUMOylation at K111 and PARylation drive accumulation at damage sites, PRMT5-mediated arginine dimethylation at R361/R586 enhances catalytic activity while coupling to ubiquitin-dependent turnover, and the deubiquitylase UCHL3 stabilizes TDP1 (PMID:19851285, PMID:20009512, PMID:22415824, PMID:24493735, PMID:29718323, PMID:29898404, PMID:35705029). Loss of TDP1 produces defective repair of TOP1- and oxidative-damage-derived breaks and age-dependent cerebellar atrophy in mice, and the homozygous active-site H493R mutation causes the neurodegenerative disorder SCAN1 by reducing catalysis and trapping a toxic covalent TDP1-DNA intermediate that additionally blocks a TDP2-dependent backup repair pathway (PMID:17914460, PMID:12244316, PMID:17948061, PMID:38761375).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 2002 High

    Established TDP1 as a PLD-superfamily enzyme and defined its two-step covalent catalytic mechanism, answering how a phosphodiesterase could cleave a protein-DNA phosphotyrosyl bond.

    Evidence Sequence analysis, HKD-motif mutagenesis and in vitro assays plus high-resolution crystal structures with transition-state analogs identifying His263 as the nucleophile

    PMID:11572945 PMID:11839309 PMID:12470949

    Open questions at the time
    • Did not establish full substrate range beyond TOP1-derived linkages
    • Did not address how the enzyme is recruited to lesions in cells
  2. 2002 High

    Linked TDP1 directly to human neurological disease by identifying the active-site H493R mutation as causative for SCAN1, establishing physiological relevance for TOP1-DNA complex repair.

    Evidence Genome-wide linkage mapping, positional cloning and protein modeling in SCAN1 families

    PMID:12244316

    Open questions at the time
    • Did not biochemically resolve whether the mutation is loss- or gain-of-function
    • Did not define the cellular repair defect
  3. 2003 High

    Showed that bulky covalent TOP1-DNA complexes must be proteolytically trimmed before TDP1 can hydrolyze the residual phosphotyrosyl linkage, defining a substrate-processing prerequisite.

    Evidence X-ray crystallography of a vanadate/DNA/TOP1-peptide quaternary transition-state mimic with human TDP1

    PMID:12618186

    Open questions at the time
    • Did not identify the protease responsible in vivo
    • Did not address mitochondrial substrates
  4. 2005 High

    Clarified the SCAN1 mechanism by showing H493R retains low residual activity but accumulates a long-lived covalent TDP1-DNA intermediate, explaining recessive inheritance and CPT hypersensitivity.

    Evidence In vitro biochemistry with wild-type and H493R protein plus camptothecin sensitivity in SCAN1 patient cells

    PMID:15920477 PMID:16141202 PMID:16935573

    Open questions at the time
    • Did not establish in vivo trapping directly
    • Did not resolve whether replication or transcription drives the lesion
  5. 2005 Medium

    Broadened TDP1 substrate scope beyond TOP1 by showing it is the principal cellular enzyme for 3'-phosphoglycolate removal and processes both single-strand and DSB ends.

    Evidence End-joining assays with SCAN1 versus normal cell extracts, recombinant TDP1 complementation, and kinetic substrate-preference analysis

    PMID:15647511 PMID:15811850

    Open questions at the time
    • In vivo physiological substrate hierarchy not established
    • Substrate preference inferred kinetically, not from cellular lesions
  6. 2006 High

    Extended TDP1 function to topoisomerase II-derived 5'-phosphotyrosyl adducts, indicating activity at the opposite DNA polarity.

    Evidence Yeast tdp1 deletion drug-sensitivity and in vitro cleavage of a 5'-phosphotyrosyl substrate

    PMID:16751265

    Open questions at the time
    • In vivo importance of TOP2 processing in mammalian cells not quantified
    • Relationship to a dedicated 5'-tyrosyl phosphodiesterase not addressed
  7. 2007 High

    Placed TDP1 within the XRCC1/DNA ligase IIIα single-strand break repair machinery and demonstrated its neuronal requirement, connecting biochemistry to organismal phenotype.

    Evidence Co-IP, in vitro activity stimulation by XRCC1/Lig3α, and a Tdp1-/- mouse with cerebellar atrophy and repair defects

    PMID:13679147 PMID:17600775 PMID:17914460

    Open questions at the time
    • Stoichiometry and architecture of the repair complex unresolved
    • Mechanism of neuronal vulnerability not defined
  8. 2007 High

    Identified ATM/DNA-PK phosphorylation at S81 as a regulatory switch that stabilizes TDP1 and drives XRCC1/Lig3α complex formation and damage-site mobilization.

    Evidence Mass spectrometry, kinase inhibition, S81A/S81E mutants, Co-IP and live-cell foci imaging

    PMID:19851285 PMID:20009512

    Open questions at the time
    • Did not establish which kinase dominates in specific lesion contexts
    • Effect on catalytic activity ruled out but downstream targets unclear
  9. 2007 High

    Provided in vivo proof that TDP1 repairs TOP1 covalent lesions and that SCAN1 is a recessive neomorphic trapping mutation.

    Evidence Tdp1-/- mouse drug-sensitivity profiling (CPT/bleomycin not etoposide) and covalent trapping of H493R in patient cells after CPT

    PMID:17948061

    Open questions at the time
    • Did not define the downstream toxicity of the trapped intermediate
    • Mild mouse phenotype left human neurodegeneration mechanism open
  10. 2009 Medium

    Showed TDP1 repairs endogenous oxidative-damage 3'-ends independently of topoisomerase I, and acts in SSB sub-pathways partially overlapping with aprataxin.

    Evidence S. pombe tdp1/pnk1 genetics with antioxidant rescue and Tdp1-/-/Aptx-/- mouse double-knockout repair assays

    PMID:19197239 PMID:19303373

    Open questions at the time
    • Division of labor between TDP1 and APTX not molecularly defined
    • Quiescent-cell findings extrapolated to neurons
  11. 2010 High

    Defined a mitochondrial role for TDP1 in base excision repair of oxidative mtDNA damage, extending its function beyond the nucleus.

    Evidence Confocal microscopy, subcellular fractionation and mitochondrial BER assays

    PMID:21041670

    Open questions at the time
    • Mitochondrial import signal/mechanism not defined
    • Mitochondrial partner proteins not identified
  12. 2010 Medium

    Implicated TDP1 in NHEJ fidelity, with its 3'-end-processing restricting error-prone insertions at DSBs.

    Evidence Yeast tdp1Δ NHEJ reporter and repair junction analysis

    PMID:20160111

    Open questions at the time
    • Mechanism inferred from yeast junctions, not reconstituted
    • Mammalian relevance not yet established at this stage
  13. 2012 High

    Consolidated TDP1 as a broad-spectrum 3'-end-processing enzyme acting on multiple adducts and defined its parallel versus epistatic relationships with CtIP for TOP1 versus TOP2 lesions.

    Evidence In vitro reconstitution with multiple substrates plus TDP1-knockout DT40 epistasis and mitochondrial activity assays

    PMID:22375014 PMID:23775789

    Open questions at the time
    • Relative in vivo contribution of each substrate class unquantified
    • Pathway choice determinants not fully resolved
  14. 2012 High

    Identified SUMOylation at K111 as a recruitment signal that concentrates TDP1 at damage sites without altering catalysis.

    Evidence Purification of SUMOylated TDP1, MS site mapping, K111R mutant repair assays

    PMID:22415824

    Open questions at the time
    • SUMO ligase responsible not identified
    • Interplay with phosphorylation not addressed here
  15. 2014 High

    Established a direct PARP1-TDP1 interaction in which PARylation, together with SUMOylation, enhances recruitment and recruits XRCC1, integrating TDP1 into PARP-signaled repair.

    Evidence TDP1/PARP1 double-knockout DT40, Co-IP, domain mapping and PARylation/foci assays

    PMID:24493735

    Open questions at the time
    • Quantitative contribution of PARylation versus SUMO to recruitment unresolved
    • Structural basis of the interaction not determined
  16. 2015 Medium

    Connected TDP1 to early NHEJ via direct XLF binding, stimulation of Ku and DNA-PK, and preferential activity on double-stranded substrates.

    Evidence In vitro pulldowns, DNA-binding and kinase activity assays of TDP1:XLF:DNA complexes

    PMID:25841101

    Open questions at the time
    • Cellular significance of the XLF interaction not yet shown at this stage
    • Single-lab biochemistry without structural validation
  17. 2017 High

    Demonstrated a cellular requirement for TDP1 in cohesive-end NHEJ and in suppressing transcription-associated TOP1-induced translocations, linking phosphorylation to NHEJ regulation.

    Evidence CRISPR TDP1-knockout HEK293 NHEJ reporters, junction analysis, S81 phosphomutants, and translocation-frequency epistasis with MRN/NHEJ

    PMID:29078113 PMID:37945566

    Open questions at the time
    • Precise step at which TDP1 acts in NHEJ assembly not resolved
    • How S81 status toggles XLF binding mechanistically not defined
  18. 2018 High

    Revealed coupled arginine-methylation regulation: PRMT5 methylation at R361/R586 boosts catalytic activity and XRCC1 recruitment, while UCHL3 deubiquitylation stabilizes TDP1, defining a PTM network controlling TDP1 levels and activity.

    Evidence PRMT5 Co-IP/MS and R361A/R586A mutants, UCHL3 depletion/overexpression with catalytic-mutant controls and ubiquitylation/turnover assays

    PMID:29718323 PMID:29898404 PMID:35705029

    Open questions at the time
    • Spatiotemporal coordination of methylation, ubiquitylation and SUMOylation unresolved
    • Disease relevance of methylation crosstalk not tested in patients
  19. 2018 Medium

    Distinguished TDP1 from Artemis in classical NHEJ of 3'-phosphoglycolate-blocked DSBs, showing distinct non-redundant end-processing functions.

    Evidence TDP1 depletion in Artemis-null cells with foci, cytogenetic and DNA-PK inhibitor analyses

    PMID:30113698

    Open questions at the time
    • Substrate determinants directing a break to TDP1 versus Artemis not defined
    • Single-lab epistasis
  20. 2019 Medium

    Defined a mitochondrial pathomechanism for SCAN1: trapped H493R-mtDNA complexes trigger Drp1 fission, block mitobiogenesis and induce PINK1-dependent mitophagy.

    Evidence mtDNA-TDP1 trapping assays, mitochondrial morphology/mitophagy imaging and mitochondria-targeted TOP1 poisons

    PMID:31723605

    Open questions at the time
    • Link between mitochondrial dysfunction and neurodegeneration not established
    • Single-lab cellular study
  21. 2022 Medium

    Extended TDP1 function to DNA-protein crosslink repair, showing it resolves abasic-site-derived 3'-PUA-peptide and histone adducts, often after proteolysis.

    Evidence Biochemical reconstitution with synthetic 3'-PUA-peptide substrates and kinetic comparison with APE1/TREX1

    PMID:35349719

    Open questions at the time
    • In vivo significance of 3'-PUA-DPC repair not established
    • Required protease for bulky DPCs not identified
  22. 2022 Medium

    Mapped the genetic landscape of TDP1 loss, identifying MUS81-dependent DSB generation and APEX1/2 synthetic lethality, framing the choice between direct resolution and HR-dependent repair of TOP1cc.

    Evidence Genome-wide CRISPR screen with co-deficient cell generation and DSB quantification

    PMID:35869071

    Open questions at the time
    • Mechanism by which MUS81 converts lesions to DSBs not detailed
    • Therapeutic exploitation of synthetic lethality not tested
  23. 2024 High

    Resolved the SCAN1 gain-of-function: H493R accumulates G1-phase transcriptional DSBs and actively blocks a TDP2-dependent backup repair pathway, distinguishing the disease mechanism from simple TDP1 loss.

    Evidence CRISPR-Cas9 human SCAN1 cell models with cell-cycle DSB, R-loop and TDP2-dependent repair assays, supported by zebrafish/human DPC studies

    PMID:37788708 PMID:38761375

    Open questions at the time
    • How the trapped intermediate physically impedes TDP2 unresolved
    • Connection of the G1 DSB phenotype to neuronal loss not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the layered PTM network and partner interactions are spatiotemporally integrated to select among TDP1's many substrates and repair pathways, and how the SCAN1 trapped intermediate causes selective neurodegeneration, remain unresolved.
  • No unified model linking PTMs to substrate/pathway choice
  • Mechanistic link from molecular trapping to neuronal death missing
  • No structure of TDP1 within its repair complexes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 6 GO:0016787 hydrolase activity 5 GO:0003677 DNA binding 2
Localization
GO:0005634 nucleus 3 GO:0005739 mitochondrion 3
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1430728 Metabolism 2
Partners
LIG3PARP1PRMT5UCHL3XLFXRCC1
Complex memberships
XRCC1/DNA ligase IIIα single-strand break repair complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TDP1 belongs to the phospholipase D (PLD) superfamily, containing two HKD signature motifs. Mutagenesis of the invariant histidines and lysines of the HKD motifs confirmed they are essential for TDP1 activity. The reaction proceeds through formation of a covalent enzyme-DNA intermediate (phosphoryl transfer mechanism common to PLD superfamily members). Sequence analysis + site-directed mutagenesis of human TDP1 + biochemical activity assays Proceedings of the National Academy of Sciences of the United States of America High 11572945
2002 Crystal structure of human TDP1 at 1.69 Å resolution reveals a monomer composed of two similar domains related by pseudo-2-fold symmetry, each contributing conserved histidine, lysine, and asparagine residues to form a single active site, confirming PLD superfamily membership and suggesting the catalytic mechanism and substrate binding mode. X-ray crystallography Structure High 11839309
2002 Crystal structures of human TDP1 bound to phosphate transition state analogs vanadate and tungstate show the inhibitor covalently bound to His263, confirming His263 as the nucleophile in the first catalytic step. Vanadate displays trigonal bipyramidal geometry mimicking the phosphodiester hydrolysis transition state. X-ray crystallography with transition state analog inhibitors Journal of molecular biology High 12470949
2002 A homozygous mutation (A1478G, H493R) in TDP1 causes SCAN1. His493 is located in the active site; protein modeling predicts disruption of the symmetric active site structure. TDP1 normally repairs covalently bound topoisomerase I-DNA complexes to prevent double-strand breaks during DNA replication. Genome-wide linkage mapping, positional cloning, protein modeling Nature genetics High 12244316
2003 Crystal structure of a transition state mimic assembled from vanadate, DNA, and a topoisomerase I-derived peptide in a quaternary complex with human TDP1 demonstrates that the topoisomerase I-DNA complex must undergo extensive modification (proteolytic trimming) before cleavage by TDP1. X-ray crystallography of quaternary transition state mimic complex Chemistry & biology High 12618186
2003 XRCC1 immunoprecipitates contain TDP1 polypeptide and TDP1 activity, establishing a physical and functional interaction between TDP1 and XRCC1. XRCC1-complemented cells repair Top1-induced DNA breaks faster and exhibit enhanced TDP1 and PNKP activities. Co-immunoprecipitation, enzymatic activity assays in XRCC1-deficient and complemented cells DNA repair Medium 13679147
2005 The SCAN1 H493R mutant TDP1 retains ~4% residual activity but accumulates a covalent TDP1-DNA intermediate with ~13 min half-life. Wild-type TDP1 can remove the stalled H493R mutant from DNA (hydrolyzing phosphohistidine linkages), explaining the recessive nature of SCAN1. TDP1 also possesses limited 3'-exonuclease activity and can remove 3'-abasic sites and 3'-biotin adducts. In vitro enzymatic assays with recombinant wild-type and H493R mutant TDP1, SCAN1 patient cell lines The Journal of biological chemistry High 16141202
2005 H493R TDP1 (SCAN1 mutant) reduces enzyme activity ~25-fold and causes accumulation of the covalent TDP1-DNA reaction intermediate. SCAN1 patient-derived cell lines are hypersensitive to camptothecin, directly implicating TDP1 in repair of CPT-induced topoisomerase I damage in human cells. Biochemical assays with purified proteins, camptothecin sensitivity assays in SCAN1 patient cell lines The EMBO journal High 15920477
2005 TDP1 is the primary enzyme responsible for 3'-phosphoglycolate (PG) removal in human cell extracts. Extracts from SCAN1 cells (H493R TDP1) fail to process 3'-PG termini on single-strand oligomers and 3' overhangs of DSBs; activity is restored by addition of recombinant TDP1. In vitro end-joining assays with cell extracts from SCAN1 patients and normal controls; complementation with recombinant TDP1 Nucleic acids research High 15647511
2005 Human TDP1 prefers single-stranded and blunt-ended duplex substrates over nicked and tailed duplex conformations for 3'-phosphotyrosyl bond hydrolysis, suggesting TDP1 acts primarily at double-strand breaks in vivo. Kinetic and binding assays with purified human TDP1 on defined DNA substrates The Journal of biological chemistry Medium 15811850
2006 TDP1 participates in repair of topoisomerase II (Top2)-mediated DNA damage in yeast. Deletion of TDP1 confers hypersensitivity to Top2-targeting agents; bacterially expressed yeast TDP1 can remove a Top2-derived peptide covalently linked to DNA via a 5'-phosphotyrosyl linkage in vitro. Genetic deletion studies in yeast, in vitro biochemical assay with 5'-phosphotyrosyl substrate Proceedings of the National Academy of Sciences of the United States of America High 16751265
2006 SCAN1 cells deficient in TDP1 (H493R) show enhanced levels of Top1 cleavage complexes and defective reversal of Top1cc after camptothecin treatment. The repair defect is not affected by aphidicolin, indicating TDP1 repairs transcription-associated Top1cc independently of replication. Top1 cleavage complex assays, camptothecin treatment, aphidicolin inhibition in SCAN1 cells DNA repair Medium 16935573
2007 TDP1 is phosphorylated at S81 by ATM and DNA-PK kinases in response to Top1-associated DNA double-strand breaks. S81 phosphorylation stabilizes TDP1 protein, induces formation of XRCC1-TDP1 complexes, and enhances mobilization of TDP1 to DNA damage sites; promotes cell survival and DNA repair. Mass spectrometry identification of phosphorylation site, kinase inhibition assays, Co-IP of TDP1-XRCC1, live-cell imaging of TDP1 foci, S81A/S81E mutant analysis The EMBO journal High 19851285
2007 TDP1 is required for efficient repair of chromosomal single-strand breaks in neurons. Tdp1-/- mice show age-dependent cerebellar atrophy; cerebellar neurons and astrocytes from Tdp1-/- mice are defective in repair of SSBs from Top1-DNA complexes and oxidative damage. Tdp1 knockout mouse generation, in vitro and in vivo SSB repair assays, histology The EMBO journal High 17914460
2007 TDP1 is associated with DNA ligase IIIα (Lig3α) and XRCC1 in the single-strand break repair machinery. TDP1 activity at abortive Top1-SSBs is stimulated by XRCC1/Lig3α in vitro. TDP1 is required for repair of ionizing radiation-induced SSBs, partly due to IR-induced protein-DNA cross-links processed by TDP1. In vitro TDP1 activity stimulation assay with XRCC1/Lig3α, γH2AX and comet assays in TDP1-deficient SCAN1 cells DNA repair Medium 17600775
2007 Tdp1-/- mice are physically, histologically, and electrophysiologically indistinguishable from wild-type but are hypersensitive to CPT and bleomycin (not etoposide). The H493R SCAN1 mutant protein becomes covalently trapped on DNA after CPT treatment in SCAN1 cells, providing direct in vivo demonstration that Tdp1 repairs Top1 covalent lesions and that SCAN1 arises from a recessive neomorphic mutation. Tdp1-/- mouse model, drug sensitivity assays, trapping assay in SCAN1 patient cells The EMBO journal High 17948061
2009 In fission yeast, Tdp1 and Pnk1 (polynucleotide kinase) process the same naturally occurring 3'-ends produced from oxidative DNA damage in quiescent (G0) cells. Tdp1 function in quiescent cells is independent of topoisomerase I, and mitochondrial respiration causes the DNA damage that Tdp1 repairs. Genetic analysis in S. pombe tdp1 and pnk1 mutants, quiescence assays, antioxidant rescue experiments The EMBO journal Medium 19197239
2009 TDP1 serine 81 phosphorylation is required for interaction with DNA ligase IIIα; S81A mutation reduces protein stability and cell survival after genotoxic stress without affecting TDP1 catalytic activity or acute repair kinetics in vivo. S81A mutant cell lines, Co-IP, clonogenic survival assays, in vitro TDP1 activity assay Cell cycle Medium 20009512
2010 TDP1 localizes to mitochondria (demonstrated by laser confocal microscopy, subcellular fractionation, and biochemical analyses). Mitochondrial base excision repair depends on TDP1 activity; TDP1 is required for efficient repair of oxidative damage in mitochondrial DNA. Confocal microscopy, subcellular fractionation, mitochondrial BER assays Proceedings of the National Academy of Sciences of the United States of America High 21041670
2010 Yeast TDP1 functions in non-homologous end joining (NHEJ) by regulating fidelity; tdp1Δ cells show high frequency of 2-4 nucleotide insertions at 5'-extension DSBs via a Ku80- and DNA ligase IV-dependent mechanism. TDP1's 3'-nucleosidase activity is proposed to generate 3'-phosphate ends that restrict polymerase access, preventing insertion errors. Yeast genetic deletion, NHEJ reporter assays, analysis of repair junctions Proceedings of the National Academy of Sciences of the United States of America Medium 20160111
2012 TDP1 repairs a broad spectrum of DNA lesions including Top1cc, Top2cc (processing 5'-phosphotyrosyl ends), 3'-phosphoglycolates, 3'-deoxyribose phosphates, and chain-terminating nucleoside analogs. TDP1-/- DT40 cells are defective in mitochondrial TDP1 activity. TDP1 and CtIP act in parallel pathways for Top1cc/MMS repair but are epistatic for Top2cc. TDP1 knockout DT40 cells, in vitro biochemical assays with recombinant human TDP1, dual knockout epistasis analysis The Journal of biological chemistry High 22375014
2012 TDP1 is SUMOylated at lysine 111 in mammalian cells. SUMOylation does not affect TDP1 catalytic activity but promotes its accumulation at DNA damage sites. A SUMOylation-deficient TDP1 (K111R) mutant displays reduced repair of chromosomal SSBs arising from transcription-associated Top1 activity or oxidative stress. Purification of SUMOylated TDP1 from mammalian cells, mass spectrometry identification of K111, K111R mutant analysis, repair assays Nature communications High 22415824
2013 TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating nucleoside analogs (CTNAs: acyclovir, cytarabine, AZT, ddC) by removing covalently linked CTNAs from DNA 3'-ends. Tdp1-/- cells are hypersensitive to ACV and Ara-C and accumulate more DNA damage; AZT and ddC treatment leads to greater mitochondrial DNA depletion in Tdp1-/- cells. In vitro TDP1 activity assays with CTNA-terminated substrates, Tdp1-/- DT40 cell sensitivity assays, mitochondrial DNA quantification Nucleic acids research High 23775789
2014 PARP1 directly binds TDP1 (N-terminal domain of TDP1 binds C-terminal domain of PARP1) and PARylates TDP1. PARylation stabilizes TDP1 together with SUMOylation and enhances TDP1 recruitment to DNA damage sites without interfering with catalytic activity. TDP1 and PARP1 are epistatic for repair of Top1cc. TDP1-PARP1 complexes recruit XRCC1. TDP1/PARP1 double-knockout DT40 cells, Co-IP of TDP1-PARP1, domain mapping, PARylation assays, DNA damage foci assays Nucleic acids research High 24493735
2015 TDP1 physically interacts with XLF and promotes assembly of NHEJ protein complexes on DNA. TDP1:XLF:DNA complexes form and XLF binding preferentially stimulates TDP1 activity on dsDNA vs. ssDNA. TDP1 also promotes DNA binding by Ku70/80 and stimulates DNA-PK activity, suggesting a role in early NHEJ. Biochemical pulldown assays, DNA-binding assays, kinase activity assays DNA repair Medium 25841101
2017 TDP1 is required for efficient NHEJ of cohesive DSBs in human cells. TDP1-KO HEK-293 cells show 5-fold reduced NHEJ repair and increased insertion events. TDP1-XLF interaction is reduced by S81A and abolished by S81E phosphomimetic mutations, linking phosphorylation status to NHEJ regulation. CRISPR/Cas9 TDP1 knockout cells, chromosomal NHEJ reporter, cell-free NHEJ assays, junction analysis, S81 phosphorylation mutants DNA repair High 29078113
2018 PRMT5 directly binds TDP1 and catalyzes symmetric arginine dimethylation at R361 and R586. R361/R586 methylation enhances TDP1 3'-phosphodiesterase activity, increases XRCC1 association with TDP1, and recruits XRCC1 to Top1cc damage foci. PRMT5 knockdown impairs TDP1 activity and increases CPT-induced DNA damage. Co-IP of PRMT5-TDP1, mass spectrometry identification of methylation sites, R361A/R586A mutant analysis, PRMT5 knockdown, DNA damage foci assays, enzymatic activity assays Nucleic acids research High 29718323
2018 UCHL3 is the deubiquitylase that controls TDP1 proteostasis. UCHL3 depletion increases TDP1 ubiquitylation and turnover; UCHL3 overexpression (but not catalytically inactive mutant) suppresses TDP1 ubiquitylation. TDP1 overexpression in rhabdomyosarcoma is driven by UCHL3 overexpression; UCHL3 is downregulated in SCAN1, causing elevated TDP1 ubiquitylation and faster turnover. UCHL3 depletion/overexpression, ubiquitylation assays, TDP1 turnover assays, catalytically inactive UCHL3 mutant Cell reports High 29898404
2019 SCAN1-TDP1 (H493R) is selectively trapped on mitochondrial DNA in regulatory non-coding and promoter regions. Trapped TDP1H493R-mtDNA complexes cause Drp1-mediated mitochondrial fission, block mitobiogenesis, and trigger PINK1-dependent mitophagy to eliminate dysfunctional mitochondria. mtDNA-TDP1 trapping assays, mitochondrial morphology imaging, mitophagy assays, mitochondrial-targeted TOP1 poison (mito-SN38) in nanoparticles Science advances Medium 31723605
2022 PRMT5-mediated R586 methylation promotes TDP1 ubiquitylation, which facilitates proteasome-dependent TDP1 turnover by impeding UCHL3 (deubiquitylase) binding to TDP1. R361 methylation enhances TDP1 3'-phosphodiesterase activity. These modifications establish mechanistic crosstalk between arginine methylation and ubiquitylation controlling TDP1 homeostasis. Arginine methylation-deficient mutants, ubiquitylation assays, UCHL3 binding assays, real-time fluorescence-based TDP1 cleavage assays, structural modeling Cell reports High 35705029
2022 Human TDP1 can repair 3'-PUA-protein DPCs (DNA-protein crosslinks arising from abasic sites) in vitro. TDP1 removes 3'-PUA-aminooxylysine-peptide adducts and directly repairs 3'-PUA-histone DPCs but not 3'-PUA-PARP1 DPCs unless proteolysis occurs first. Kinetic constants were determined for multiple substrate configurations. Biochemical reconstitution with synthetic 3'-PUA-peptide substrates, kinetic analysis, comparison with APE1 and TREX1 Nucleic acids research Medium 35349719
2022 MUS81 is a key factor that mediates generation of excess DSBs in TDP1 KO cells (via CRISPR screens). APEX1/2 are synthetic lethal with TDP1 but APEX1/2 deficiency does not reduce DSB formation in TDP1 KO cells. TOP1cc can be either resolved directly by TDP1 or converted into DSBs repaired by homologous recombination. Whole-genome CRISPR screen, co-deficient cell generation, DSB quantification assays Nature communications Medium 35869071
2024 SCAN1 (H493R TDP1) cells accumulate TOP1ccs and transcriptional DSBs specifically in G1 phase, due to increased DSB formation from abortive removal of transcription-blocking TOP1ccs. The mutant TDP1 protein actively hampers DSB repair via a TDP2-dependent backup pathway (gain of function), distinct from simple loss of TDP1 activity. CRISPR-Cas9 human SCAN1 cell models, TOP1cc assays, DSB quantification in cell cycle phases, R-loop analysis, TDP2-dependent repair assays Cell reports High 38761375
2014 Drosophila TDP1 gene glaikit (gkt) encodes the functional ortholog of human TDP1; protein extracts from gkt mutant flies are defective in hydrolyzing 3'-DNA-tyrosyl residues. Loss of gkt causes reduced lifespan, diminished climbing ability, and sensitivity to bleomycin and Top1 poisons; all phenotypes are rescued by neuronal expression of TDP1. Drosophila PiggyBac insertion mutant, in vitro TDP1 activity assay in fly extracts, behavioral assays, neuronal rescue experiments Proceedings of the National Academy of Sciences of the United States of America Medium 25331878
2009 Loss of both TDP1 and aprataxin (APTX) in mouse neural cells synergistically slows global repair of oxidative and alkylation-induced SSBs, but not CPT-induced Top1-SSBs (which accumulate equally in Tdp1-/- and Tdp1-/-/Aptx-/- astrocytes), placing TDP1 and APTX in partially overlapping but distinct SSB repair sub-pathways. Tdp1-/-/Aptx-/- double knockout mouse, quantitative SSB repair assays in quiescent astrocytes DNA repair Medium 19303373
2018 TDP1 and Artemis are epistatic for repair of 3'-phosphoglycolate-terminated DSBs by classical NHEJ. A TDP1 deficiency (but not Artemis deficiency) results in increased dicentric chromosomes following neocarzinostatin treatment, whereas Artemis deficiency results in unrepaired DSBs (53BP1 foci). TDP1 and Artemis perform distinct functions in C-NHEJ of terminally blocked DSBs. TDP1 knockout/knockdown in Artemis-null cells, γH2AX and 53BP1 foci, cytogenetic analysis, DNA-PK inhibitor studies Nucleic acids research Medium 30113698
2017 TDP1 suppresses chromosomal translocations arising from TOP1-induced DSBs during gene transcription. These translocations involve the MRN complex and canonical NHEJ. TDP1-dependent end-joining protects gene transcription and genome stability. TDP1 mutant/deletion cells, translocation frequency assays, epistasis with MRN and NHEJ factors Nature communications Medium 37945566
2023 TDP1 and SPRTN repair endogenous, CPT-induced, and formaldehyde-induced DNA-protein crosslinks including histone H3-DPCs and TOP1-DPCs. Resolution of H3-DNA crosslinks requires upstream proteolysis by SPRTN followed by peptide removal by TDP1 in RPE1 cells and zebrafish embryos. SPRTN and TDP1 function in different pathways for endogenous TOP1-DPCs. TDP2 expression is increased in TDP1-deficient cells/embryos. TDP1 and SPRTN knockouts in human cells and zebrafish, DPC quantification with antibodies, TDP2 expression analysis Open biology Medium 37788708

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nature genetics 415 12244316
2014 Tyrosyl-DNA-phosphodiesterases (TDP1 and TDP2). DNA repair 271 24856239
2001 The tyrosyl-DNA phosphodiesterase Tdp1 is a member of the phospholipase D superfamily. Proceedings of the National Academy of Sciences of the United States of America 239 11572945
2005 Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages. The Journal of biological chemistry 195 16141202
2007 TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. The EMBO journal 184 17914460
2002 Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage. Proceedings of the National Academy of Sciences of the United States of America 183 12368472
2014 PARP1-TDP1 coupling for the repair of topoisomerase I-induced DNA damage. Nucleic acids research 182 24493735
2005 SCAN1 mutant Tdp1 accumulates the enzyme--DNA intermediate and causes camptothecin hypersensitivity. The EMBO journal 180 15920477
2003 Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions. DNA repair 166 13679147
2012 Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells. The Journal of biological chemistry 153 22375014
2002 The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1. Structure (London, England : 1993) 144 11839309
2002 Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1. Proceedings of the National Academy of Sciences of the United States of America 141 12397185
2005 Deficiency in 3'-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic acids research 134 15647511
2009 Optimal function of the DNA repair enzyme TDP1 requires its phosphorylation by ATM and/or DNA-PK. The EMBO journal 130 19851285
2006 Tyrosyl-DNA phosphodiesterase (Tdp1) participates in the repair of Top2-mediated DNA damage. Proceedings of the National Academy of Sciences of the United States of America 129 16751265
2004 TDP1 overexpression in human cells counteracts DNA damage mediated by topoisomerases I and II. The Journal of biological chemistry 128 15494395
2007 Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? The EMBO journal 122 17948061
2010 Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria. Proceedings of the National Academy of Sciences of the United States of America 115 21041670
2003 Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide. Chemistry & biology 115 12618186
2002 Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures. Journal of molecular biology 106 12470949
2012 TDP2 promotes repair of topoisomerase I-mediated DNA damage in the absence of TDP1. Nucleic acids research 95 22740648
2007 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 89 17576665
2006 Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA repair 85 16935573
2013 TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs. Nucleic acids research 83 23775789
2011 Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) inhibitors. Expert opinion on therapeutic patents 75 21843105
2009 Synergistic decrease of DNA single-strand break repair rates in mouse neural cells lacking both Tdp1 and aprataxin. DNA repair 72 19303373
2012 SUMO modification of the neuroprotective protein TDP1 facilitates chromosomal single-strand break repair. Nature communications 71 22415824
2007 TDP1 facilitates repair of ionizing radiation-induced DNA single-strand breaks. DNA repair 68 17600775
2018 PRMT5-mediated arginine methylation of TDP1 for the repair of topoisomerase I covalent complexes. Nucleic acids research 65 29718323
2014 TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA. The EMBO journal 63 25391662
2012 Synthesis and biological evaluation of the first dual tyrosyl-DNA phosphodiesterase I (Tdp1)-topoisomerase I (Top1) inhibitors. Journal of medicinal chemistry 63 22536944
2014 Clinical and cellular roles for TDP1 and TOP1 in modulating colorectal cancer response to irinotecan. Molecular cancer therapeutics 61 25522766
2012 Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span. The Journal of biological chemistry 59 22232551
2012 Synthesis and biological evaluation of indenoisoquinolines that inhibit both tyrosyl-DNA phosphodiesterase I (Tdp1) and topoisomerase I (Top1). Journal of medicinal chemistry 55 23259865
2010 TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell cycle (Georgetown, Tex.) 55 20009512
2006 TDP1-dependent DNA single-strand break repair and neurodegeneration. Mutagenesis 55 16775218
2006 Increased expression and activity of repair genes TDP1 and XPF in non-small cell lung cancer. Lung cancer (Amsterdam, Netherlands) 55 17118488
2013 TDP1 deficiency sensitizes human cells to base damage via distinct topoisomerase I and PARP mechanisms with potential applications for cancer therapy. Nucleic acids research 54 24335147
2005 Substrate specificity of tyrosyl-DNA phosphodiesterase I (Tdp1). The Journal of biological chemistry 52 15811850
2018 UCHL3 Regulates Topoisomerase-Induced Chromosomal Break Repair by Controlling TDP1 Proteostasis. Cell reports 51 29898404
2019 SCAN1-TDP1 trapping on mitochondrial DNA promotes mitochondrial dysfunction and mitophagy. Science advances 49 31723605
2013 TDP1 is an HMG chromatin protein facilitating RNA polymerase I transcription in African trypanosomes. Nucleic acids research 49 23361461
2009 Tdp1 protects against oxidative DNA damage in non-dividing fission yeast. The EMBO journal 49 19197239
2009 4-Pregnen-21-ol-3,20-dione-21-(4-bromobenzenesulfonate) (NSC 88915) and related novel steroid derivatives as tyrosyl-DNA phosphodiesterase (Tdp1) inhibitors. Journal of medicinal chemistry 46 19883083
2018 Discovery, Synthesis, and Evaluation of Oxynitidine Derivatives as Dual Inhibitors of DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1), and Potential Antitumor Agents. Journal of medicinal chemistry 45 30336023
2015 Synthesis and biological evaluation of nitrated 7-, 8-, 9-, and 10-hydroxyindenoisoquinolines as potential dual topoisomerase I (Top1)-tyrosyl-DNA phosphodiesterase I (TDP1) inhibitors. Journal of medicinal chemistry 45 25811317
2009 In vitro complementation of Tdp1 deficiency indicates a stabilized enzyme-DNA adduct from tyrosyl but not glycolate lesions as a consequence of the SCAN1 mutation. DNA repair 43 19211312
2022 TDP1-independent pathways in the process and repair of TOP1-induced DNA damage. Nature communications 41 35869071
2017 Synthesis and Biological Evaluation of the First Triple Inhibitors of Human Topoisomerase 1, Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), and Tyrosyl-DNA Phosphodiesterase 2 (Tdp2). Journal of medicinal chemistry 41 28418653
2015 TDP1 promotes assembly of non-homologous end joining protein complexes on DNA. DNA repair 39 25841101
2014 Identification of a putative Tdp1 inhibitor (CD00509) by in vitro and cell-based assays. Journal of biomolecular screening 39 25117203
2004 The role of TDP1 from budding yeast in the repair of DNA damage. DNA repair 38 15135727
2019 Identification of a ligand binding hot spot and structural motifs replicating aspects of tyrosyl-DNA phosphodiesterase I (TDP1) phosphoryl recognition by crystallographic fragment cocktail screening. Nucleic acids research 36 31199869
2017 TDP1 is required for efficient non-homologous end joining in human cells. DNA repair 36 29078113
2013 Real-time detection of TDP1 activity using a fluorophore-quencher coupled DNA-biosensor. Biosensors & bioelectronics 36 23693093
2019 New Hydrazinothiazole Derivatives of Usnic Acid as Potent Tdp1 Inhibitors. Molecules (Basel, Switzerland) 35 31619021
2013 TDP1 and PARP1 deficiency are cytotoxic to rhabdomyosarcoma cells. Molecular cancer research : MCR 34 23913164
2010 Yeast Tdp1 regulates the fidelity of nonhomologous end joining. Proceedings of the National Academy of Sciences of the United States of America 34 20160111
2015 Abacavir, an anti-HIV-1 drug, targets TDP1-deficient adult T cell leukemia. Science advances 33 26601161
2013 Epigenetic and genetic inactivation of tyrosyl-DNA-phosphodiesterase 1 (TDP1) in human lung cancer cells from the NCI-60 panel. DNA repair 31 24355542
2017 Subfunctionalization of duplicate MYB genes in Solanum commersonii generated the cold-induced ScAN2 and the anthocyanin regulator ScAN1. Plant, cell & environment 30 28386931
2021 Effect of Pterostilbene, a Natural Derivative of Resveratrol, in the Treatment of Colorectal Cancer through Top1/Tdp1-Mediated DNA Repair Pathway. Cancers 29 34439157
2020 Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs topoisomerase 1 DNA-protein crosslinks and 3'-blocking lesions in the absence of tyrosyl-DNA phosphodiesterase 1 (TDP1). DNA repair 29 32460231
2014 TDP1/TOP1 Ratio as a Promising Indicator for the Response of Small Cell Lung Cancer to Topotecan. Journal of cancer science & therapy 29 25232464
2022 Human TDP1, APE1 and TREX1 repair 3'-DNA-peptide/protein cross-links arising from abasic sites in vitro. Nucleic acids research 28 35349719
2019 The Protease WSS1A, the Endonuclease MUS81, and the Phosphodiesterase TDP1 Are Involved in Independent Pathways of DNA-protein Crosslink Repair in Plants. The Plant cell 27 30760561
2018 Synthesis and evaluation of aryliden- and hetarylidenfuranone derivatives of usnic acid as highly potent Tdp1 inhibitors. Bioorganic & medicinal chemistry 27 30076000
2017 TDP1 is Critical for the Repair of DNA Breaks Induced by Sapacitabine, a Nucleoside also Targeting ATM- and BRCA-Deficient Tumors. Molecular cancer therapeutics 27 28802254
2021 Synthesis of Methoxy-, Methylenedioxy-, Hydroxy-, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer. Journal of medicinal chemistry 24 34008967
2020 The First Berberine-Based Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), an Important DNA Repair Enzyme. International journal of molecular sciences 24 32998385
2018 TDP1 suppresses mis-joining of radiomimetic DNA double-strand breaks and cooperates with Artemis to promote optimal nonhomologous end joining. Nucleic acids research 23 30113698
2018 A polysaccharide from Antrodia cinnamomea mycelia exerts antitumor activity through blocking of TOP1/TDP1-mediated DNA repair pathway. International journal of biological macromolecules 22 30267816
2020 Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1. Molecules (Basel, Switzerland) 20 32751997
2014 Identification of novel PARP inhibitors using a cell-based TDP1 inhibitory assay in a quantitative high-throughput screening platform. DNA repair 20 24794403
2017 Identification of Natural Products That Inhibit the Catalytic Function of Human Tyrosyl-DNA Phosphodiesterase (TDP1). SLAS discovery : advancing life sciences R & D 19 28697309
2016 Isoeugenol is a selective potentiator of camptothecin cytotoxicity in vertebrate cells lacking TDP1. Scientific reports 19 27220325
2014 Biochemical assays for the discovery of TDP1 inhibitors. Molecular cancer therapeutics 19 25024006
2021 Dysregulation of MicroRNAs and PIWI-Interacting RNAs in a Caenorhabditis elegans Parkinson's Disease Model Overexpressing Human α-Synuclein and Influence of tdp-1. Frontiers in neuroscience 18 33762903
2021 Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs. Oncology and therapy 18 34159519
2021 New Hybrid Compounds Combining Fragments of Usnic Acid and Thioether Are Inhibitors of Human Enzymes TDP1, TDP2 and PARP1. International journal of molecular sciences 18 34768766
2024 TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks. Cell reports 17 38761375
2022 Post-translational regulation of Tyrosyl-DNA phosphodiesterase (TDP1 and TDP2) for the repair of the trapped topoisomerase-DNA covalent complex. DNA repair 17 35101776
2022 Interplay between symmetric arginine dimethylation and ubiquitylation regulates TDP1 proteostasis for the repair of topoisomerase I-DNA adducts. Cell reports 17 35705029
2015 Tyrosyl-DNA-phosphodiesterase I (TDP1) participates in the removal and repair of stabilized-Top2α cleavage complexes in human cells. Mutation research 17 26421495
2021 Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments. Molecules (Basel, Switzerland) 16 34073771
2019 Novel Inhibitors of DNA Repair Enzyme TDP1 Combining Monoterpenoid and Adamantane Fragments. Anti-cancer agents in medicinal chemistry 16 30523770
2015 A Theoretical Study of Phosphoryl Transfers of Tyrosyl-DNA Phosphodiesterase I (Tdp1) and the Possibility of a "Dead-End" Phosphohistidine Intermediate. Biochemistry 16 26121557
2014 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 16 25331878
2017 HTLV-1 bZIP factor suppresses TDP1 expression through inhibition of NRF-1 in adult T-cell leukemia. Scientific reports 15 28993637
2014 Development of an oligonucleotide-based fluorescence assay for the identification of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors. Analytical biochemistry 15 24637157
2013 The role of TDP1 and APTX in mitochondrial DNA repair. Biochimie 15 24161509
2021 Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development. Science advances 14 33514542
2023 Tyrosyl-DNA phosphodiesterase 1 (TDP1) and SPRTN protease repair histone 3 and topoisomerase 1 DNA-protein crosslinks in vivo. Open biology 13 37788708
2023 TDP-1 and FUST-1 co-inhibit exon inclusion and control fertility together with transcriptional regulation. Nucleic acids research 12 37587694
2023 TDP1 suppresses chromosomal translocations and cell death induced by abortive TOP1 activity during gene transcription. Nature communications 12 37945566
2017 Synthesis, anti-cancer screening and tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition activity of novel piperidinyl sulfamides. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 12 29037996
2013 Tracking the processing of damaged DNA double-strand break ends by ligation-mediated PCR: increased persistence of 3'-phosphoglycolate termini in SCAN1 cells. Nucleic acids research 12 24371269
2020 Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1. Melanoma research 10 31626034
2024 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 9 38279210
2020 TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy. Cancers 9 32028591

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