ArticleNature structural & molecular biology2012
Mechanism of repair of 5'-topoisomerase II-DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2.
Article in Nature structural & molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- Spinocerebellar ataxia, autosomal recessive type 23 (SCAR23) with compound TDP2 variants: clinical, molecular, and quantitative follow-up.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes.Mini reviews in medicinal chemistry · 2025Review
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Tyrosyl-DNA phosphodiesterase 2 (Tdp2) repairs DNA-protein crosslinks and protects against double strand breaksFrontiers in cell and developmental biology · 2024Article
- Article
- Inactivating TDP2 missense mutation in siblings with congenital abnormalities reminiscent of fanconi anemia.Human genetics · 2023Article
- Chromosomal Rearrangements and Chromothripsis: The Alternative End Generation Model.International journal of molecular sciences · 2023Review
- Molecular basis for processing of topoisomerase 1-triggered DNA damage by Apn2/APE2.Cell reports · 2022Article
- Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes.Science advances · 2021Article
- Topoisomerase-Mediated DNA Damage in Neurological Disorders.Frontiers in aging neuroscience · 2021Review
- Small Molecule Inhibitors Confirm Ubiquitin-Dependent Removal of TOP2-DNA Covalent Complexes.Molecular pharmacology · 2020Article
- Ubiquitin stimulated reversal of topoisomerase 2 DNA-protein crosslinks by TDP2.Nucleic acids research · 2020Article
- Endogenous DNA 3' Blocks Are Vulnerabilities for BRCA1 and BRCA2 Deficiency and Are Reversed by the APE2 Nuclease.Molecular cell · 2020Article
- Excision repair of topoisomerase DNA-protein crosslinks (TOP-DPC).DNA repair · 2020Review
- GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.Developmental cell · 2020Article
- Molecular mechanisms of topoisomerase 2 DNA-protein crosslink resolution.Cellular and molecular life sciences : CMLS · 2020Review
- Novel deazaflavin tyrosyl-DNA phosphodiesterase 2 (TDP2) inhibitors.DNA repair · 2020Article
- Virological Basis for the Cure of Chronic Hepatitis B.ACS infectious diseases · 2019Review
- Effect of TDP2 on the Level of TOP2-DNA Complexes and SUMOylated TOP2-DNA Complexes.International journal of molecular sciences · 2018Article
- New fluorescence-based high-throughput screening assay for small molecule inhibitors of tyrosyl-DNA phosphodiesterase 2 (TDP2).European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts. Here, X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 β-2-helix-β DNA damage-binding 'grasp', helical 'cap' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove. The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing. Structural, mutational and functional analyses support a single-metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase (EEP) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs.
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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.