scholarly journals Simulation of DNA Supercoil Relaxation

2016 ◽  
Vol 110 (10) ◽  
pp. 2176-2184 ◽  
Author(s):  
Ikenna D. Ivenso ◽  
Todd D. Lillian
Keyword(s):  
Supercoil Relaxation

scholarly journals Single-molecule imaging of DNA gyrase activity in livingEscherichia coli

2018 ◽  
Author(s):  
Mathew Stracy ◽  
Adam J.M. Wollman ◽  
Elzbieta Kaja ◽  
Jacek Gapinski ◽  
Ji-Eun Lee ◽  
...  
Keyword(s):  
Single Molecule ◽  
High Speed ◽  
Replication Fork ◽  
Dna Gyrase ◽  
Chromosomal Dna ◽  
Replication Fork Progression ◽  
Dna Strands ◽  
Steady State Levels ◽  
Negative Supercoiling ◽  
Supercoil Relaxation

ABSTRACTBacterial DNA gyrase introduces negative supercoils into chromosomal DNA and relaxes positive supercoils introduced by replication and transiently by transcription. Removal of these positive supercoils is essential for replication fork progression and for the overall unlinking of the two duplex DNA strands, as well as for ongoing transcription. To address how gyrase copes with these topological challenges, we used high-speed single-molecule fluorescence imaging in liveEscherichia colicells. We demonstrate that at least 300 gyrase molecules are stably bound to the chromosome at any time, with ∼12 enzymes enriched near each replication fork. Trapping of reaction intermediates with ciprofloxacin revealed complexes undergoing catalysis. Dwell times of ∼2 s were observed for the dispersed gyrase molecules, which we propose maintain steady-state levels of negative supercoiling of the chromosome. In contrast, the dwell time of replisome-proximal molecules was ∼8 s, consistent with these catalyzing processive positive supercoil relaxation in front of the progressing replisome.

scholarly journals 1H-Benzimidazole derivatives as mammalian DNA topoisomerase I inhibitors.

2007 ◽  
Vol 54 (3) ◽  
pp. 561-565 ◽  
Author(s):  
A Selcen Alpan ◽  
H Semih Gunes ◽  
Zeki Topcu
Keyword(s):  
Topoisomerase I ◽  
Biological Properties ◽  
Benzimidazole Derivatives ◽  
Type I ◽  
Mass Spectral Data ◽  
Dna Topoisomerase ◽  
Mass Spectral ◽  
Elemental Analyses ◽  
Supercoil Relaxation

Benzimidazole is one of the most important heterocyclic groups manifesting various biological properties, such as antibacterial, antifungal, antimicrobial, antiprotozoal and antihelmintic activities. Several benzimidazole derivatives are also active as inhibitors of type I DNA topoisomerases. In this study, three 1H-benzimidazole derivatives with different electronic characteristics at position 5-, namely 5-chloro-4-(1H-benzimidazole-2-yl)phenol (Cpd I), 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) and 4-(1H-benzimidazole-2-yl)phenol (Cpd III), were synthesized and evaluated for their effects on mammalian type I DNA topoisomerase activity using quantitative in vitro plasmid supercoil relaxation assays. For the structure elucidation of the compounds, melting points, UV, IR, 1H NMR, 13C NMR, mass spectral data and elemental analyses were interpreted. Among the compounds, 5-methyl-4-(1H-benzimidazole-2-yl)phenol (Cpd II) manifested relatively potent topoisomerase I inhibition.

scholarly journals Chromatin Architectural Factors as Safeguards against Excessive Supercoiling during DNA Replication

2020 ◽  
Vol 21 (12) ◽  
pp. 4504
Author(s):  
Syed Moiz Ahmed ◽  
Peter Dröge
Keyword(s):  
Dna Replication ◽  
Protein Complexes ◽  
Genome Replication ◽  
Relaxation Rates ◽  
Architectural Features ◽  
Genome Wide ◽  
New Findings ◽  
Accessory Factors ◽  
Novel Strategy ◽  
Supercoil Relaxation

Key DNA transactions, such as genome replication and transcription, rely on the speedy translocation of specialized protein complexes along a double-stranded, right-handed helical template. Physical tethering of these molecular machines during translocation, in conjunction with their internal architectural features, generates DNA topological strain in the form of template supercoiling. It is known that the build-up of transient excessive supercoiling poses severe threats to genome function and stability and that highly specialized enzymes—the topoisomerases (TOP)—have evolved to mitigate these threats. Furthermore, due to their intracellular abundance and fast supercoil relaxation rates, it is generally assumed that these enzymes are sufficient in coping with genome-wide bursts of excessive supercoiling. However, the recent discoveries of chromatin architectural factors that play important accessory functions have cast reasonable doubts on this concept. Here, we reviewed the background of these new findings and described emerging models of how these accessory factors contribute to supercoil homeostasis. We focused on DNA replication and the generation of positive (+) supercoiling in front of replisomes, where two accessory factors—GapR and HMGA2—from pro- and eukaryotic cells, respectively, appear to play important roles as sinks for excessive (+) supercoiling by employing a combination of supercoil constrainment and activation of topoisomerases. Looking forward, we expect that additional factors will be identified in the future as part of an expanding cellular repertoire to cope with bursts of topological strain. Furthermore, identifying antagonists that target these accessory factors and work synergistically with clinically relevant topoisomerase inhibitors could become an interesting novel strategy, leading to improved treatment outcomes.

scholarly journals Dynamics of DNA Supercoil Relaxation by Type II Topoisomerases

2011 ◽  
Vol 100 (3) ◽  
pp. 192a
Author(s):  
Qing Shao ◽  
David Dunlap ◽  
Laura Finzi
Keyword(s):  
Type Ii ◽  
Supercoil Relaxation

scholarly journals Single-Molecule Supercoil Relaxation Assay as a Screening Tool to Determine the Mechanism and Efficacy of Human Topoisomerase IB Inhibitors

2015 ◽  
Vol 14 (11) ◽  
pp. 2552-2559 ◽  
Author(s):  
Yeonee Seol ◽  
Hongliang Zhang ◽  
Keli Agama ◽  
Nicholas Lorence ◽  
Yves Pommier ◽  
...  
Keyword(s):  
Single Molecule ◽  
Screening Tool ◽  
Topoisomerase Ib ◽  
Supercoil Relaxation

scholarly journals Flavonoids in Helichrysum pamphylicum Inhibit Mammalian Type I DNA Topoisomerase

2008 ◽  
Vol 63 (1-2) ◽  
pp. 69-74 ◽  
Author(s):  
Zeki Topcu ◽  
Bintug Ozturk ◽  
Ozlem Kucukoglu ◽  
Emrah Kilinc
Keyword(s):  
Antioxidant Capacity ◽  
Topoisomerase I ◽  
Type I ◽  
Dna Topoisomerase I ◽  
Dependent Manner ◽  
Dna Topoisomerase ◽  
Total Antioxidant ◽  
Supercoil Relaxation ◽  
Dose Dependent

DNA topoisomerases are important targets for cancer chemotherapy. We investigated the effects of a methanolic extract of Helichrysum pamphylicum on mammalian DNA topoisomerase I via in vitro plasmid supercoil relaxation assays. The extracts manifested a considerable inhibition of the enzyme’s activity in a dose-dependent manner. We also performed a HPLC analysis to identify the flavonoid content of the H. pamphylicum extract and tested the identified flavonoids; luteolin, luteolin-4-glucoside, naringenin, helichrysinA and isoquercitrin, on DNA topoisomerase I activity. The measurement of the total antioxidant capacity of the flavonoid standards suggested that the topoisomerase inhibition might be correlated with the antioxidant capacity of the plant.

VacciniaDNA Topoisomerase I:  Evidence Supporting a Free Rotation Mechanism for DNA Supercoil Relaxation†

Biochemistry ◽  
1997 ◽  
Vol 36 (17) ◽  
pp. 5212-5222 ◽  
Author(s):  
James T. Stivers ◽  
Thomas K. Harris ◽  
Albert S. Mildvan
Keyword(s):  
Topoisomerase I ◽  
Free Rotation ◽  
Supercoil Relaxation

Biological Activity of 1-Aryl-3-phenethylamino-1-propanone Hydrochlorides and 3-Aroyl-4-aryl-1-phenethyl-4-piperidinols on PC-3 Cells and DNA Topoisomerase I Enzyme

2010 ◽  
Vol 65 (11-12) ◽  
pp. 647-652 ◽  
Author(s):  
Ebru Mete ◽  
Halise Inci Gul ◽  
Pakize Canturk ◽  
Zeki Topcu ◽  
Bulbul Pandit ◽  
...  
Keyword(s):  
Biological Activity ◽  
Phenyl Ring ◽  
Topoisomerase I ◽  
Mannich Bases ◽  
Type I ◽  
Average Value ◽  
Cytotoxic Compounds ◽  
Type I Topoisomerases ◽  
Supercoil Relaxation ◽  
Anticonvulsant Activities

1aA number of studies reported Mannich bases to manifest antimicrobial, cytotoxic, anticancer, anti-inflammatory, and anticonvulsant activities. A considerable number of therapeutically important cytotoxic compounds are active on DNA topoisomerases that regulate the DNA topology. In the present study we evaluated the biological activity of mono- Mannich bases, 1-aryl-3-phenethylamino-1-propanone hydrochlorides (- 10a), and semicyclic mono- Mannich bases, 3-aroyl-4-aryl-1-phenethyl-4-piperidinols (1b - 9b), synthesized in our laboratory. We employed androgen-independent human prostate cancer cells (PC-3) to assess the cytotoxicity of the compounds and extended the biological activity evaluation to cover supercoil relaxation assays of mammalian type I topoisomerases. Our results showed that the compounds had cytotoxicity within the 8.2 - 32.1 μM range, while two compounds gave rise to a comparable average value in topo I interference of 42% and 40% for 10a (with a hydroxy substituent on the phenyl ring from mono-Mannich bases) and 5b (with a fluoro substituent on the phenyl ring from the semicyclic mono-Mannich base series, piperidinols), respectively

Ozenoxacin: A Novel Drug Discovery for the Treatment of Impetigo

2019 ◽  
Vol 16 (3) ◽  
pp. 259-264 ◽  
Author(s):  
Jagdish K. Sahu ◽  
Arun K. Mishra
Keyword(s):  
Mechanism Of Action ◽  
Bacterial Infections ◽  
Dna Gyrase ◽  
The United States ◽  
Present Review ◽  
Topoisomerase Iv ◽  
Gyrase A ◽  
Chromosomal Condensation ◽  
Supercoil Relaxation ◽  
Novel Drug

Objective: Ozenoxacin is one of the potent quinolone antibiotics, recently approved by the United States Food and Drug Administration (USFDA) with reported pharmacology to treat the impetigo. The demand for better acting topical formulation is increasing day by day. The present review is an attempt to summarize the facts behind the chemistry and biological applications of Ozenoxacin. Mechanism of Action: This novel drug being a quinolone antibiotic compound, acts by inhibiting DNA gyrase A and topoisomerase IV and affects supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation and many others. Mechanism of Action: This novel drug being a quinolone antibiotic compound, acts by inhibiting DNA gyrase A and topoisomerase IV and affects supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation and many others. Pharmacology: Ozenoxacin has demonstrated to have a bactericidal activity against organisms, such as Staphylococcus aureus and Staphylococcus pyogenes. Ozenoxacin is non-fluorinated quinolone and being developed for the other dermatological bacterial infections as well. No sign of genotoxicity was observed when tested experimentally. Conclusion: The present review also covers the complete picture of pharmacokinetics, clinical trials, toxicity and future scope and possible avenues in this arena.

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