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Category: TopoGEN Blog

Topo I and Cobalt Complex

Topo I and Cobalt Complex

Revealing new paper on metallo-inhibitors. Article Source: Science Direct Synthesis and structure elucidation of a cobalt(II) complex as topoisomerase I inhibitor: In vitro DNA binding, nuclease and RBC hemolysis Abstract Metal-based cancer chemotherapeutic agent of the type Co(II) complex [Co(mpca)2]·H2O (1), where, Hmpca = 9-methyl-[1,10]phenanthroline-2-carboxylic acid was synthesized and characterized by various spectroscopic and analytical techniques and further authenticated by single crystal X-ray diffraction methods. In vitro DNA binding studies of complex 1 with CT DNA was carried out by…

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Supercoiling DNA with Reverse Gyrase

Supercoiling DNA with Reverse Gyrase

A new reverse gyrase from Pyrobaculum species has been identified with some novel properties. It combines helicase with topoisomerase domains. Very interesting from an evolutionary perspective. Article Source: The Journal of Biological Chemistry The reverse gyrase form Pyrobaculum calidifontis, a novel extremely thermophilic DNA topoisomerase endowed with DNA unwinding and annealing activities Abstract Reverse gyrase is a DNA topoisomerase specific of hyperthermophilic bacteria and archaea. It catalyses the peculiar ATP-dependent DNA positive supercoiling reaction and might be involved in the…

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Topoisomerase Inhibition and Torsional Stress

Topoisomerase Inhibition and Torsional Stress

Topology is critical in allowing chromatin to function in a normal manner. DNA templating is clearly impacted when enzymes that relieve strain are blocked in a chromatin context. Specifically, inhibition of topoisomerases leads to rapid accumulation of torsional strain accompanied by changes in Pol II kinetics and destabilization of nucleosomes. Transcription-generated torsional stress destabilizes nucleosomes Article Source: Nature Abstract As RNA polymerase II (Pol II) transcribes a gene, it encounters an array of well-ordered nucleosomes. How it traverses through this…

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Embryogenesis and Topo I: Screening for Cheaters

Embryogenesis and Topo I: Screening for Cheaters

The authors have used a clever genetic screen to identify “Cheater mutations” in genes that confer the ability of cells to behave in a non-cooperative fashion in a tissue context. These cheater cells could for example, outgrow surrounding cells as aberrant clones, and thereby derail a tightly regulated process of differentiation that is pivotal in development. A very nice bioinformatic rendering of the data revealed that an axis of regulatory genes that are under the influence of topoisomerase I and…

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Mutations and Drug Resistance: Topo I and Irinotecan

Mutations and Drug Resistance: Topo I and Irinotecan

Low efficacy of a particular class of anti-cancer agents is discussed in this article. The authors hypothesize that Topoisomerase I mutations cause a resistance to Irinotecan, a commonly used drug for the treatment of colon cancer. Article Source: Molecular Cancer New Topoisomerase I mutations are associated with resistance to camptothecin Abstract Background: Topoisomerase I (TOP1) is a nuclear enzyme that catalyzes the relaxation of supercoiled DNA during DNA replication and transcription. TOP1 is the molecular target of camptothecin and related…

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Quantifying Topo Action in E. Coli

Quantifying Topo Action in E. Coli

A new method to quantify endogenous Topoisomerase action in E. coli cells is nicely described in this paper. The technique is based on the In Vivo Link Kit, also known as the ICE bioassay. Article Source: American Society for Microbiology Isolation and Quantitation of Topoisomerase Complexes Accumulated on Escherichia coli Chromosomal DNA Abstract DNA topoisomerases are important targets in anticancer and antibacterial therapy because drugs can initiate cell death by stabilizing the transient covalent topoisomerase-DNA complex. In this study, we…

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Topo II and Topo I are not Equivalent Topological Adjustment Machines in vivo

Topo II and Topo I are not Equivalent Topological Adjustment Machines in vivo

In a recent report in Nucleic Acids Research, researchers provide evidence that topoisomerase I and II perform similar functions in vitro (relaxation of supercoiled DNA); however, the in vivo situation is very different. There are of course non-overlapping activities of type I and II enzymes, specifically, the latter are cell cycle regulated and provide decatenase activity which is essential for life. Still, topo enzymes provide other key functions that attend all aspects of template activation. From genetic complementation studies, topological…

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Study Aims to Broaden Understanding of The Propagation of Topological Domains in Eukaryotes

Study Aims to Broaden Understanding of The Propagation of Topological Domains in Eukaryotes

In this paper researchers have devised a very clever strategy to evaluate the genesis of topological domains. The basic idea is to design high affinity DNA binding sites for specific proteins as tandem copies within a single plasmid. Then, they tested whether it was possible to divide the plasmid into protein defined domains of constrained topological segments (or create topological barriers). This is a nice inroad to understand how topological domains can be propagated in linear chromosomes in eukaryotes. In…

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Astrazeneca Compounds Target Topoisomerases in vivo

Astrazeneca Compounds Target Topoisomerases in vivo

Kinase inhibitors are an important class of anticancer and anti-inflammatory compounds. Pharmaceutical companies rely on structure activity-genotoxicity evaluations to evaluate off target action of novel drugs (such Ames or other in vitro genotoxicity screens). Effective drugs should be highly targeted and not pleiotropic. Researchers at AstraZeneca have recently shown that promising compounds (that hit the desired target and appear to be non-genotoxic) may target topoisomerases in vivo or show other DNA reactive characteristics. Off target drug action is extremely important…

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