ArticleThe Journal of biological chemistry2014
Proteolytic degradation of topoisomerase II (Top2) enables the processing of Top2·DNA and Top2·RNA covalent complexes by tyrosyl-DNA-phosphodiesterase 2 (TDP2).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 118 citations in OpenAlex.
- TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.Nature communications · 2025Article
- Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Article
- MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.Cell death & disease · 2024Article
- RAD54L2 counters TOP2-DNA adducts to promote genome stability.Science advances · 2023Article
- RAD54L2-mediated DNA damage avoidance pathway specifically preserves genome integrity in response to topoisomerase 2 poisons.Science advances · 2023Article
- The abscission checkpoint senses chromatin bridges through Top2α recruitment to DNA knots.The Journal of cell biology · 2023Article
- Replication-associated formation and repair of human topoisomerase IIIα cleavage complexes.Nature communications · 2023Article
- Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway.International journal of molecular sciences · 2023Article
- A CRISPR-Cas9 screen identifies EXO1 as a formaldehyde resistance gene.Nature communications · 2023Article
- ATM inhibitor KU60019 synergistically sensitizes lung cancer cells to topoisomerase II poisons by multiple mechanisms.Scientific reports · 2023Article
- Genetic Ablation of the DNA Damage Response Pathway Attenuates Lamin-Associated Dilated Cardiomyopathy in Mice.JACC. Basic to translational science · 2022Article
- Untangling the roles of TOP2A and TOP2B in transcription and cancer.Science advances · 2022Review
- The repair of topoisomerase 2 cleavage complexes in Arabidopsis.The Plant cell · 2022Article
- 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
- Jadomycins: A potential chemotherapy for multi-drug resistant metastatic breast cancer.Pharmacology research & perspectives · 2021Review
- The Epstein-Barr virus deubiquitinating enzyme BPLF1 regulates the activity of topoisomerase II during productive infection.PLoS pathogens · 2021Article
- Evaluation of repair activity by quantification of ribonucleotides in the genome.Genes to cells : devoted to molecular & cellular mechanisms · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Eukaryotic type II topoisomerases (Top2α and Top2β) are homodimeric enzymes; they are essential for altering DNA topology by the formation of normally transient double strand DNA cleavage. Anticancer drugs (etoposide, doxorubicin, and mitoxantrone) and also Top2 oxidation and DNA helical alterations cause potentially irreversible Top2·DNA cleavage complexes (Top2cc), leading to Top2-linked DNA breaks. Top2cc are the therapeutic mechanism for killing cancer cells. Yet Top2cc can also generate recombination, translocations, and apoptosis in normal cells. The Top2 protein-DNA covalent complexes are excised (in part) by tyrosyl-DNA-phosphodiesterase 2 (TDP2/TTRAP/EAP2/VPg unlinkase). In this study, we show that irreversible Top2cc induced in suicidal substrates are not processed by TDP2 unless they first undergo proteolytic processing or denaturation. We also demonstrate that TDP2 is most efficient when the DNA attached to the tyrosyl is in a single-stranded configuration and that TDP2 can efficiently remove a tyrosine linked to a single misincorporated ribonucleotide or to polyribonucleotides, which expands the TDP2 catalytic profile with RNA substrates. The 1.6-Å resolution crystal structure of TDP2 bound to a substrate bearing a 5'-ribonucleotide defines a mechanism through which RNA can be accommodated in the TDP2 active site, albeit in a strained conformation.
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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.