Abstract
Single-stranded breaks in the DNA backbone caused by many endogenous and exogenous agents often lead to double-stranded breaks that are known causes of chromosomal instabilities leading to copious diseases. We describe a label-free detection technique using two-dimensional (2D) solid-state nanopore field-effect transistors (FETs) to sense and map site-specific nicks in the DNA backbone. We use all-atom molecular dynamics simulations coupled with electronic transport modeling to illustrate the 2D membrane device capability to sense minute structural changes of any translocating biomolecules via their in-plane electronic sheet current signatures, whereas Van der Waals analyses explain the distinct hydrophobic interactions between various DNA-nick types with graphene and MoS2 nanopore membranes. Specifically, we describe the atypical unzipping behavior of DNA strands caused by the biomolecule sticking at nicked site in the graphene nanopore, under the influence of voltage-specific translocations.
Highlights
DNA damages in the form of single-stranded breaks (SSBs) and double-stranded breaks (DSBs) occur daily in every cell due to many endogenous and exogenous factors[1]
Exogenous agents such as ionizing radiation, UV radiation, and other environmental chemical sources are known to induce oxidation of DNA nucleotides leading to SSBs and DSBs8
We show the number of transversal nucleotides that have passed through the pore during the entire nanopore field-effect transistors (FETs)
Summary
DNA damages in the form of single-stranded breaks (SSBs) and double-stranded breaks (DSBs) occur daily in every cell due to many endogenous and exogenous factors[1]. Various DNA repair pathways subjected to different lesions are activated by the cell to counteract the damages induced to the DNA1 Though these repair mechanisms efficiently fix the continuously occurring damages, some unrepaired SSBs get converted into DSBs resulting in genomic instabilities that are known to promote cancer and/or cell apoptosis[9,10]. One notices that before membrane devices to distinguish amongst nicks created between 5 ns and after 8 ns, the nucleotides translocate through the pore, different pairs of nucleotides at various sites along the DNA continuously, but within the 5–8 ns time window, the nucleotide backbone In this context, we describe the anomalous behavior of number fluctuates around 10/11 at the nick position, so no nicked dsDNA that unlike with MoS2 membrane unzip in graphene nanopores at voltage-specific nick sites during the translocation is taking place. The DNA conformational variations arising from the interaction between the biomolecule and the graphene membrane
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