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Soni, G. V.

Publications and source records attributed to Soni, G. V..

2 recordsLinked to original sources

Reversible DNA Translocation as a molecular caliper to probe the nanoscale asymmetry of glass nanopores

Studying DNA conformation is crucial for understanding gene regulation, chromatin structure, and genomic stability. Nanopores have proven to be excellent label-free, high-throughput tools for studying conformational changes in various biomolecular structures. Conical glass nanopores are widely used in solid-state nanopore studies due to their simple and cost-effective fabrication. However, their inherent geometric asymmetry introduces distinct characteristics in the translocation dynamics of DNA. Here, we demonstrate bi-directional translocation of multiple DNA lengths through a conical nanopore to understand the role of pore asymmetry. We show a quantitative comparison of various parameters, such as the conductance drop ({Delta}G), translocation time ({Delta}t), event charge deficit (ECD) and percentage of DNA folding in both directions. A natural output of our ECD-based analysis is the estimation of the effective sensing length of our conical pore geometry. In the nanoscale regime, sensing length controls spatial resolution of the nanopore detector and is challenging to measure. Our study reveals significant experimental insights into the dependence of DNA length, translocation directionality, and applied voltage on the translocation mechanism, contributing to a broader utilization of glass nanopores in sensing technologies. TOC Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=119 SRC="FIGDIR/small/664396v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@9afdc7org.highwire.dtl.DTLVardef@18b3f36org.highwire.dtl.DTLVardef@e2f825org.highwire.dtl.DTLVardef@11177db_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

Nanopore Assay for Fingerprinting DNA Binding and Quantifying Real-Time Cleavage by Catalytically Active Cas9 Enzyme

Nanopore sensing, a high-resolution DNA sequencing technology, is fast expanding into novel and exciting direction of probing specific DNA-enzyme interactions. Although proven excellent for detection of structural features of bare DNA, quantitative measurements on enzyme-DNA complexes and its real-time activity are lagging and only starting to emerge for long DNA templates. Signal-to-noise requirement and high translocation speeds make it difficult to detect protein bound on biologically relevant plasmid length DNA. To this end we report accurate position detection of a catalytically active Cas9 bound to its single or multiple target sites on the DNA. Protein position is fingerprinted using event charge deficit (ECD) based analysis of the high signal-to-noise electrical signals as the complex translocates through a glass nanopore. Using a time dependent assay, we quantify kinetics of the released products upon enzymatic cleavage of the target DNA by the wild-type Cas9 nuclease. Our approach enables the nanopore based single molecule sensing of DNA-protein complexes, for real-time monitoring of biochemical reactions. This may help understand protein binding & localization as well as improve Cas9 based targeting in genome engineering applications. TOC Figure O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/656938v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@9ea40org.highwire.dtl.DTLVardef@f214e6org.highwire.dtl.DTLVardef@13a10bborg.highwire.dtl.DTLVardef@12067ab_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗