ArticleDNA repair2015
TDP1 promotes assembly of non-homologous end joining protein complexes on DNA.
Article in DNA repair, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Persistent TOP1 cleavage complexes in drug-tolerant cells drive adaptive resistance to EGFR-targeted therapies in lung cancer.Science advances · 2026Article
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 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
- 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
- N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells.Scientific reports · 2023Article
- Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.Oncology and therapy · 2021Article
- A Dual-Sensor-Based Screening System for In Vitro Selection of TDP1 Inhibitors.Sensors (Basel, Switzerland) · 2021Article
- SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance.Cell death & disease · 2021Article
- Exonuclease 1 (Exo1) Participates in Mammalian Non-Homologous End Joining and Contributes to Drug Resistance in Ovarian Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Inhibition of HMGB1 Overcomes Resistance to Radiation and Chemotherapy in Nasopharyngeal Carcinoma.OncoTargets and therapy · 2020Article
- Tyrosyl-DNA phosphodiesterases are involved in mutagenic events at a ribonucleotide embedded into DNA in human cells.PloS one · 2020Article
- End Processing Factor APLF Promotes NHEJ Efficiency and Contributes to TMZ- and Ionizing Radiation-Resistance in Glioblastoma Cells.OncoTargets and therapy · 2020Article
- DNA damage response and repair in perspective: Aedes aegypti, Drosophila melanogaster and Homo sapiens.Parasites & vectors · 2019Review
- Tyrosyl-DNA Phosphodiesterase I N-Terminal Domain Modifications and Interactions Regulate Cellular Function.Genes · 2019Review
- Induction Of XLF And 53BP1 Expression Is Associated With Temozolomide Resistance In Glioblastoma Cells.OncoTargets and therapy · 2019Article
- Identification Of Natural Compound Derivative For Inhibition Of XLF And Overcoming Chemoresistance In Colorectal Cancer Cells.Drug design, development and therapy · 2019Article
- Nonhomologous end joining key factor XLF enhances both 5-florouracil and oxaliplatin resistance in colorectal cancer.OncoTargets and therapy · 2019Article
- TDP1 suppresses mis-joining of radiomimetic DNA double-strand breaks and cooperates with Artemis to promote optimal nonhomologous end joining.Nucleic acids research · 2018Article
- A mechanism for semaphorin-induced apoptosis: DNA damage of endothelial and myogenic cells in primary cultures from skeletal muscle.Oncotarget · 2018Article
- Tyrosyl-DNA phosphodiesterases: rescuing the genome from the risks of relaxation.Nucleic acids research · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The repair of DNA double-strand breaks (DSB) is central to the maintenance of genomic integrity. In tumor cells, the ability to repair DSBs predicts response to radiation and many cytotoxic anti-cancer drugs. DSB repair pathways include homologous recombination and non-homologous end joining (NHEJ). NHEJ is a template-independent mechanism, yet many NHEJ repair products carry limited genetic changes, which suggests that NHEJ includes mechanisms to minimize error. Proteins required for mammalian NHEJ include Ku70/80, the DNA-dependent protein kinase (DNA-PKcs), XLF/Cernunnos and the XRCC4:DNA ligase IV complex. NHEJ also utilizes accessory proteins that include DNA polymerases, nucleases, and other end-processing factors. In yeast, mutations of tyrosyl-DNA phosphodiesterase (TDP1) reduced NHEJ fidelity. TDP1 plays an important role in repair of topoisomerase-mediated DNA damage and 3'-blocking DNA lesions, and mutation of the human TDP1 gene results in an inherited human neuropathy termed SCAN1. We found that human TDP1 stimulated DNA binding by XLF and physically interacted with XLF to form TDP1:XLF:DNA complexes. TDP1:XLF interactions preferentially stimulated TDP1 activity on dsDNA as compared to ssDNA. TDP1 also promoted DNA binding by Ku70/80 and stimulated DNA-PK activity. Because Ku70/80 and XLF are the first factors recruited to the DSB at the onset of NHEJ, our data suggest a role for TDP1 during the early stages of mammalian NHEJ.
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Registered trials
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.