New modulated design and synthesis of chiral CuII/SnIV bimetallic potential anticancer drug entity: In vitro DNA binding and pBR322 DNA cleavage activity

2012 ◽  
Vol 90 ◽  
pp. 208-217 ◽  
Author(s):  
Sartaj Tabassum ◽  
Girish Chandra Sharma ◽  
Farukh Arjmand
Keyword(s):  
Dna Binding ◽  
Anticancer Drug ◽  
Dna Cleavage ◽  
Design And Synthesis ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Pbr322 Dna

Synthesis and Characterisation of RuII Polypyridyl Complexes: DNA-Binding, Photocleavage, and Topoisomerase I and II Inhibitory Activity

2013 ◽  
Vol 66 (11) ◽  
pp. 1406 ◽  
Author(s):  
Xiaojun He ◽  
Guang Yang ◽  
Xiaonan Sun ◽  
Lingjun Xie ◽  
Lifeng Tan
Keyword(s):  
Dna Binding ◽  
Dna Cleavage ◽  
Topoisomerase I ◽  
Mixed Ligand ◽  
Dual Inhibitor ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Pbr322 Dna ◽  
Dna Strand ◽  
Strand Passage

Two mixed-ligand ruthenium(ii) complexes [Ru(phen)2(cptcp)]2+ (Ru1; phen = 1,10-phenanthroline, cptcp = 2-(4-carbazol-9-yl-phenyl)-1H-1,3,7,8-tetraaza-cyclopenta-[l]-phenanthrene) and [Ru(phen)2(btcpc)]2+ (Ru2; btcpc = 9-butyl-6-(1H-1,3,7,8-tetraaza-cyclo-cyclopenta-[l]-phenanthren-2-yl)-9H-carbazole-3-carbaldehyde) have been synthesised and characterised. The DNA-binding behaviours of the two complexes have been investigated by using spectroscopic and viscosity measurements. Results suggest that the two complexes bind to DNA by intercalation. The photocleavage of plasmid pBR322 DNA indicates that Ru1 exhibits more effective DNA cleavage activity in comparison to that exhibited by Ru2 under the same conditions, and different cleavage mechanisms are determined. Topoisomerase inhibition and DNA strand passage assay confirm that Ru1 may act as an efficient dual inhibitor of topoisomerases I and II, whereas Ru2 may only act as a single inhibitor of topoisomerases II.

scholarly journals Correction to Metal-Based Netropsin Mimics Showing AT-Selective DNA Binding and DNA Cleavage Activity at Red Light

2019 ◽  
Vol 58 (14) ◽  
pp. 9514-9514
Author(s):  
Ashis K. Patra ◽  
Tuhin Bhowmick ◽  
Suryanarayanarao Ramakumar ◽  
Akhil R. Chakravarty
Keyword(s):  
Dna Binding ◽  
Dna Cleavage ◽  
Red Light ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Selective Dna Binding

scholarly journals 5’ modifications to CRISPR Cas9 gRNA can change the dynamics and size of R-loops and inhibit DNA cleavage

2020 ◽  
Author(s):  
Grace Mullally ◽  
Kara van Aelst ◽  
Mohsin M. Naqvi ◽  
Fiona M. Diffin ◽  
Tautvydas Karvelis ◽  
...  
Keyword(s):  
Single Molecule ◽  
Dna Cleavage ◽  
Rna Aptamers ◽  
Loop Formation ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Rnp Complex ◽  
Target Binding ◽  
The Impact

A key aim in exploiting CRISPR-Cas is the engineering of gRNA to introduce additional functionalities, ranging from small nucleotide changes that increase efficiency of on-target binding to the inclusion of large functional RNA aptamers and ribonucleoproteins (RNPs. Interactions between gRNA and Cas9 are crucial for RNP complex assembly but several distinct regions of the gRNA are amenable to modification. Using a library of modified gRNAs, we used in vitro ensemble and single-molecule assays to assess the impact of RNA structural alterations on RNP complex formation, R-loop dynamics, and endonuclease activity. Our results indicate that R-loop formation and DNA cleavage activity are essentially unaffected by gRNA modifications of the Upper Stem, first Hairpin and 3’ end. In contrast, 5’ additions of only two or three nucleotides reduced R-loop formation and cleavage activity of the RuvC domain relative to a single nucleotide addition. Such gRNA modifications are a common by-product of in vitro transcribed gRNA. We also observed that addition of a 20 nt RNA hairpin to the 5’ end supported formation of a stable ~9 bp R-loop that could not activate DNA cleavage. These observations will assist in successful gRNA design.

Metal-Based Netropsin Mimics Showing AT-Selective DNA Binding and DNA Cleavage Activity at Red Light

2007 ◽  
Vol 46 (22) ◽  
pp. 9030-9032 ◽  
Author(s):  
Ashis K. Patra ◽  
Tuhin Bhowmick ◽  
Suryanarayanarao Ramakumar ◽  
Akhil R. Chakravarty
Keyword(s):  
Dna Binding ◽  
Dna Cleavage ◽  
Red Light ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Selective Dna Binding

scholarly journals DNA binding induces a cis-to-trans switch in Cre recombinase to enable intasome assembly

2020 ◽  
Vol 117 (40) ◽  
pp. 24849-24858
Author(s):  
Aparna Unnikrishnan ◽  
Carlos Amero ◽  
Deepak Kumar Yadav ◽  
Kye Stachowski ◽  
Devante Potter ◽  
...  
Keyword(s):  
Dna Binding ◽  
Protein Interactions ◽  
Dna Cleavage ◽  
Conformational Dynamics ◽  
Dna Recombination ◽  
Cre Recombinase ◽  
Protein Protein Interactions ◽  
Cleavage Activity ◽  
Dna Cleavage Activity ◽  
Synaptic Complexes

Mechanistic understanding of DNA recombination in the Cre-loxP system has largely been guided by crystallographic structures of tetrameric synaptic complexes. Those studies have suggested a role for protein conformational dynamics that has not been well characterized at the atomic level. We used solution nuclear magnetic resonance (NMR) spectroscopy to discover the link between intrinsic flexibility and function in Cre recombinase. Transverse relaxation-optimized spectroscopy (TROSY) NMR spectra show the N-terminal and C-terminal catalytic domains (CreNTD and CreCat) to be structurally independent. Amide 15N relaxation measurements of the CreCat domain reveal fast-timescale dynamics in most regions that exhibit conformational differences in active and inactive Cre protomers in crystallographic tetramers. However, the C-terminal helix αN, implicated in assembly of synaptic complexes and regulation of DNA cleavage activity via trans protein–protein interactions, is unexpectedly rigid in free Cre. Chemical shift perturbations and intra- and intermolecular paramagnetic relaxation enhancement (PRE) NMR data reveal an alternative autoinhibitory conformation for the αN region of free Cre, wherein it packs in cis over the protein DNA binding surface and active site. Moreover, binding to loxP DNA induces a conformational change that dislodges the C terminus, resulting in a cis-to-trans switch that is likely to enable protein–protein interactions required for assembly of recombinogenic Cre intasomes. These findings necessitate a reexamination of the mechanisms by which this widely utilized gene-editing tool selects target sites, avoids spurious DNA cleavage activity, and controls DNA recombination efficiency.

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