ArticleNucleic acids research2011
The geometry of DNA supercoils modulates the DNA cleavage activity of human topoisomerase I.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- The mismatch repair endonuclease MutLα tethers duplex regions of DNA together and relieves DNA torsional tension.Nucleic acids research · 2023Article
- Unraveling topoisomerase IA gate dynamics in presence of PPEF and its preclinical evaluation against multidrug-resistant pathogens.Communications biology · 2023Article
- Structural insights into catalytical capability for CPT11 hydrolysis and substrate specificity of a novel marine microbial carboxylesterase, E93.Frontiers in microbiology · 2022Article
- Lipid-derived electrophiles mediate the effects of chemotherapeutic topoisomerase I poisons.Cell chemical biology · 2021Article
- Microbiota-Host-Irinotecan Axis: A New Insight Toward Irinotecan Chemotherapy.Frontiers in cellular and infection microbiology · 2021Review
- Neutral Porphyrin Derivative Exerts Anticancer Activity by Targeting Cellular Topoisomerase I (Top1) and Promotes Apoptotic Cell Death without Stabilizing Top1-DNA Cleavage Complexes.Journal of medicinal chemistry · 2018Article
- Molecular biological tools applied for identification of mastitis causing pathogens.International journal of veterinary science and medicine · 2017Review
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- The dynamic interplay between DNA topoisomerases and DNA topology.Biophysical reviews · 2016Review
- DNA Interaction Studies of Selected Polyamine Conjugates.International journal of molecular sciences · 2016Article
- The Dynamic Interplay Between DNA Topoisomerases and DNA Topology.Biophysical reviews · 2016Article
- Poisoning of mitochondrial topoisomerase I by lamellarin D.Molecular pharmacology · 2014Article
- Are other fluorescent tags used instead of ethidium bromide safer?Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2013Article
- Article
- A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Collaborating functions of BLM and DNA topoisomerase I in regulating human rDNA transcription.Mutation researchArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Human topoisomerase I plays an important role in removing positive DNA supercoils that accumulate ahead of replication forks. It also is the target for camptothecin-based anticancer drugs that act by increasing levels of topoisomerase I-mediated DNA scission. Evidence suggests that cleavage events most likely to generate permanent genomic damage are those that occur ahead of DNA tracking systems. Therefore, it is important to characterize the ability of topoisomerase I to cleave positively supercoiled DNA. Results confirm that the human enzyme maintains higher levels of cleavage with positively as opposed to negatively supercoiled substrates in the absence or presence of anticancer drugs. Enhanced drug efficacy on positively supercoiled DNA is due primarily to an increase in baseline levels of cleavage. Sites of topoisomerase I-mediated DNA cleavage do not appear to be affected by supercoil geometry. However, rates of ligation are slower with positively supercoiled substrates. Finally, intercalators enhance topoisomerase I-mediated cleavage of negatively supercoiled substrates but not positively supercoiled or linear DNA. We suggest that these compounds act by altering the perceived topological state of the double helix, making underwound DNA appear to be overwound to the enzyme, and propose that these compounds be referred to as 'topological poisons of topoisomerase I'.
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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.