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220 results for “Topoisomerase”
DNA-stimulated liquid-liquid phase separation by eukaryotic topoisomerase II modulates catalytic function
<p>Type II topoisomerases modulate chromosome supercoiling, condensation, and catenation by moving one double-stranded DNA segment through a transient break in a second duplex. How DNA strands are chosen and selectively passed to yield appropriate topological outcomes – e.g., decatenation vs. catenation – is poorly understood. Here we show that at physiological enzyme concentrations, eukaryotic type IIA topoisomerases (topo IIs) readily coalesce into condensed bodies. DNA stimulates condensation and fluidizes these assemblies to impart liquid-like behavior. Condensation induces both budding yeast and human topo IIs to switch from DNA unlinking to active DNA catenation, and depends on an unstructured C-terminal region, the loss of which leads to high levels of knotting and reduced catenation. Our findings establish that local protein concentration and phase separation can regulate how topo II creates or dissolves DNA links, behaviors that can account for the varied roles of the enzyme in supporting transcription, replication, and chromosome compaction.</p>
DNA-stimulated liquid-liquid phase separation by eukaryotic topoisomerase II modulates catalytic function
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Topoisomerase IIA is essential for maintenance of mitotic chromosome structure
<p>Data files for the manuscript #2020-01760 "Topoisomerase IIA is essential for maintenance of mitotic chromosome structure" in press in the journal "Preceedings of the National Academy of Sciences" (PNAS).</p> <p> </p> <p>Abstract</p> <p>Topoisomerase IIa (TOP2A) is a core component of mitotic chromosomes and important for establishing mitotic chromosome condensation. The primary roles of TOP2A in mitosis have been difficult to decipher due to its multiple functions across the cell cycle. To more precisely understand the role of TOP2A in mitosis, we used the auxin inducible degron (AID) system to rapidly degrade the protein at different stages of the human cell cycle. Removal of TOP2A prior to mitosis does not affect prophase timing or the initiation of chromosome condensation. Instead, it prevents chromatin condensation in prometaphase, extends the length of prometaphase and ultimately causes cells to exit mitosis without chromosome segregation occurring. Surprisingly, we find that removal of TOP2A from cells arrested in prometaphase or metaphase cause dramatic loss of compacted mitotic chromosome structure and conclude that TOP2A is crucial for maintenance of mitotic chromosomes. Treatments with drugs used to poison/inhibit TOP2A function, such as etoposide and ICRF-193, does not phenocopy the effects on chromosome structure of TOP2A degradation by AID. Our data, points to a role for TOP2A as a structural chromosome maintenance enzyme component locking in condensation states once sufficient compaction is achieved.</p>
Insights into the DNA and RNA Interactions of Human Topoisomerase III Beta Using Molecular Dynamics Simulations
<p>hTOP3 simulations for both covalently and non-covalently bound DNA and RNA substrates. Simulation times = 300ns, with 1/ns per frame = 300 frames each.</p>
Study of Sequential Topoisomerase, Irinotecan/Oxaliplatin - Etoposide /Carboplatin in Extensive Small Cell Lung Cancer (SCLC)
ClinicalTrials.gov study NCT00240097. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Data for paper "Characterization of new, efficient Mycobacterium tuberculosis topoisomerase-I inhibitors..."
<p>FILES containd dataset for paper:</p> <p><strong>Characterization of new, efficient <em>Mycobacterium tuberculosis</em> topoisomerase-I inhibitors and their interaction with human ABC multidrug transporters</strong></p> <p> </p> <p>Csilla Temesszentandrási-Ambrus<sup>1,2</sup>, Balázs Sarkadi<sup>1</sup>, Gergely Szakács<sup>1</sup>, Szilárd Tóth<sup>1</sup>, László Őrfi<sup>3,4</sup>, Csaba Szántai-Kis<sup>3</sup>, Péter Bánhegyi<sup>3</sup>, István Szabadkai<sup>3</sup>, Ferenc Baska<sup>3</sup>, Ruben C. Hartkoorn<sup>5</sup>, Rinkee Verma<sup>6</sup>, Valakunja Nagaraja<sup>6</sup>, Mary A Lingerfelt <sup>7</sup>, Sean Ekins<sup>7</sup> and Ágnes Telbisz<sup>1,*</sup></p> <p> </p> <p>This work is dedicated to late Prof. György Kéri, founder and CEO of Vichem Ltd.</p> <p> </p> <p><sup>1</sup> Institute of Enzymology, RCNS-HAS, Budapest, Hungary</p> <p><sup>2</sup> Molecular Medicine Doctoral School, Semmelweis University, Budapest, Hungary</p> <p><sup>3</sup> Vichem Chemie Research Ltd., Budapest, Hungary.</p> <p><sup>4 </sup>Department of Pharmaceutical Chemistry, Semmelweis University, Budapest, Hungary</p> <p><sup>5</sup> Chemical Biology of Antibiotics, Center for Infection and Immunity, Inserm, CNRS, Institut Pasteur de Lille, Université de Lille, Lille, France</p> <p><sup>6</sup> Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India</p> <p><sup>7</sup> Collaborations Pharmaceuticals, Inc., 840 Main Campus Drive, Lab 3510, Raleigh, USA</p> <p> </p> <p> </p> <p>*Corresponding author:</p> <p>e-mail: telbisz.agnes@ttk.mta.hu<br> </p>
IP-MS, MeCP2 Represses the Activity of Topoisomerase IIβ in Long Neuronal Genes
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Two type I topoisomerases maintain DNA topology in human mitochondria
<p>Raw image data from the article "Two type I topoisomerases maintain DNA topology in human mitochondria" by Katja E. Menger et al.</p>
Dataset for: Modeling Allosteric Mechanisms of Eukaryotic Type II Topoisomerases
<p>The set of molecular dynamics trajectories generated and analyzed in the paper "Modeling Allosteric Mechanisms of Eukaryotic Type II Topoisomerases." <strong>Citations should refer directly to the manuscript. </strong> </p> <p>The uploaded zip file "trajectory_data.zip" contains trajectories for the (1) ATP (2) ADP (3) Apo (4) D26N (5) R1128G and (6) D26N/R1128G h3k9ac systems. In each directory is 5 XTC files, which correspond to the trajectories for the 5 different simulations performed for each system, along with an AMBER-formated PRMTOP file. Solvent molecules were removed from each file, and trajectories were strided such that there is one frame per 100 ps. </p>
Transcriptional repression by a secondary DNA binding surface of DNA topoisomerase I safeguards against transcription overdrive
<p>Molecular dynamics simulation input files and processed output trajectories.</p>
Epirubicin or Not in Patients With TOP2A (Topoisomerase (DNA) II Alpha (170kD)) Normal Early Breast Cancer
ClinicalTrials.gov study NCT00689156. IPD Sharing: Not stated. Countries: 1. Publications: 6.
Topoisomerase II phylogenies
<p>Topoisomerase II phylogenies</p>
Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency
GEO Series GSE133954. Mus musculus. 4 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Distinct effects of topoisomerase II inhibitors on tumor cell lines (part 1)
GEO Series GSE33624. Homo sapiens. 14 samples. Type: Expression profiling by array.
Type II topoisomerases shape multi-scale 3D chromatin folding in regions of positive supercoils (LaminB1 CnR).
GEO Series GSE255734. Homo sapiens. 6 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Effects of DNA topoisomerase inhibitor acriflavine on endothelial gene expression and chromatin accessibility (ATAC-Seq)
GEO Series GSE176554. Homo sapiens. 2 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Osmotic disruption of chromatin induces Topoisomerase 2 activity at sites of transcriptional stress [Mnase-Seq]
GEO Series GSE280155. Saccharomyces cerevisiae. 16 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Topoisomerase IIA in Adult NSCs Regulates SVZ Neurogenesis by Transcriptional Activation of Usp37 (ChIP-Seq)
GEO Series GSE192397. Mus musculus. 2 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
Co-ordinate inhibition of autism candidate genes by topoisomerase inhibitors
GEO Series GSE43900. Mus musculus; Homo sapiens. 70 samples. Type: Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by array.
MeCP2 Represses the Activity of Topoisomerase IIb in Long Neuronal Genes [RNA-Seq]
GEO Series GSE246461. Mus musculus. 20 samples. Type: Expression profiling by high throughput sequencing.
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