scholarly journals Topoisomerase I-mediated DNA Cleavage Induced by the Minor Groove-directed Binding of Bibenzimidazoles to a Distal Site

2007 ◽  
Vol 365 (3) ◽  
pp. 561-569 ◽  
Author(s):  
Qasim A. Khan ◽  
Daniel S. Pilch
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase I ◽  
Minor Groove ◽  
Distal Site

scholarly journals DNA sequence selectivity of human topoisomerase I-mediated DNA cleavage induced by camptothecin

2009 ◽  
Vol 18 (6) ◽  
pp. 1326-1331
Author(s):  
Chandanamali Punchihewa ◽  
Megan Carver ◽  
Danzhou Yang
Keyword(s):  
Dna Sequence ◽  
Dna Cleavage ◽  
Topoisomerase I ◽  
Sequence Selectivity

Minor groove dimeric bisbenzimidazoles inhibit in vitro DNA binding to eukaryotic DNA topoisomerase I

2010 ◽  
Vol 75 (6) ◽  
pp. 695-701 ◽  
Author(s):  
O. Yu. Susova ◽  
A. A. Ivanov ◽  
S. S. Morales Ruiz ◽  
E. A. Lesovaya ◽  
A. V. Gromyko ◽  
...  
Keyword(s):  
Dna Binding ◽  
Topoisomerase I ◽  
Minor Groove ◽  
Dna Topoisomerase I ◽  
Dna Topoisomerase ◽  
Dimeric Bisbenzimidazoles ◽  
Eukaryotic Dna

scholarly journals DNA Minor Groove Binding with Bisbenzamidine-Ru(II) Complexes

2019 ◽  
Author(s):  
Mateo I. Sánchez ◽  
Gustavo Rama ◽  
Renata Calo ◽  
Kübra Ucar ◽  
Per Lincoln ◽  
...  
Keyword(s):  
Dna Cleavage ◽  
Coordination Compounds ◽  
Photophysical Properties ◽  
Organic Ligand ◽  
Minor Groove ◽  
The Other ◽  
Minor Groove Binding ◽  
Binding Agent ◽  
Groove Binding ◽  
Dna Minor Groove

We report the first Ru(II) coordination compounds that interact with DNA through a canonical minor groove insertion mode and with selectivity for A/T rich sites. This was made possible by integrating a bis‑benzamidine minor groove DNA-binding agent with a ruthenium(II) complex. Importantly, one of the enantiomers (Δ‑[Ru(bpy)<sub>2</sub><b>b4bpy</b>]<sup>2+</sup>, <b>Δ‑4Ru</b>) shows a considerably higher DNA affinity than the parent organic ligand and than the other enantiomer, particularly for the AATT sequence, while the other enantiomer preferentially targets long AAATTT sites with overall lower affinity. Finally, we demonstrate that the photophysical properties of these new binders can be exploited for DNA cleavage using visible light.

scholarly journals Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation

2013 ◽  
Vol 41 (22) ◽  
pp. 10110-10123 ◽  
Author(s):  
Jessica Marinello ◽  
Giovanni Chillemi ◽  
Susana Bueno ◽  
Stefano G. Manzo ◽  
Giovanni Capranico
Keyword(s):  
Dna Cleavage ◽  
Topoisomerase I ◽  
Cpg Island ◽  
Loop Formation ◽  
Antisense Transcripts ◽  
Cleavage Complex

Molecular Beacon Enables Combination of Highly Processive and Highly Sensitive Rolling Circle Amplification Readouts for Detection of DNA-Modifying Enzymes

Nano LIFE ◽  
2015 ◽  
Vol 05 (02) ◽  
pp. 1541002 ◽  
Author(s):  
Emil L. Kristoffersen ◽  
Maria Gonzalez ◽  
Magnus Stougaard ◽  
Cinzia Tesauro
Keyword(s):  
Real Time ◽  
Dna Cleavage ◽  
Topoisomerase I ◽  
Drug Response ◽  
Molecular Beacon ◽  
Rolling Circle Amplification ◽  
Dna Topoisomerase ◽  
Rolling Circle ◽  
Topoisomerase Ib ◽  
Highly Sensitive

Here we present an optimized readout format for detection of the circularized products from a DNA-based sensor for measurement of DNA-modifying enzymes including DNA Topoisomerase I. The basic design of the DNA-sensor relies on the use of a substrate that can be circularized by the activity of DNA-modifying enzymes like type IB Topoisomerases and subsequently amplified by a rolling circle amplification (RCA) mechanism. The RCA process can be followed in real-time by the addition of a molecular beacon with a fluorophore/quencher pair. Upon hybridization to the amplified product, the fluorophore/quencher pair is separated, giving rise to a fluorescent signal, measurable in pseudo real-time using a qPCR machine or in a fluorimeter. The RCA products in complex with the molecular beacon can subsequently be moved to microscopic slides and analyzed in a fluorescence microscope. We describe the proof of the principle of this molecular beacon-based method combining the qPCR readout format with the standard Rolling circle Enhanced Enzymatic Assay previously reported. Although the qPCR setup is less sensitive, it allows easy, fast, and high-throughput measurement of enzyme activities. Human Topoisomerase IB (TopIB) is a well-known target for the clinically used anticancer drugs of the camptothecin family. The cytotoxic effect of camptothecins correlates directly with the intracellular TopIB activity affecting reversibly the Topoisomerase/DNA cleavage complexes. Therefore, we envisioned that the presented method may find use for the prediction of cellular drug response and for drug screening to discover novel molecules that specifically inhibit TopIB or other DNA-modifying enzymes.

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