Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regeneration of Burnt Bridges on a DNA Catenane Walker

ABSTRACT: Abstract DNA walkers are molecular machines that can move with high precision onthe nanoscale due to their structural and functional programmability. Despite recent advances in the field that allow exploring different energy sources, stimuli, and mechanisms of action for these nanomachines, the continuous operation and reusability of DNA walkers remains challenging because in most cases the steps, once taken by the walker, cannot be taken again. Herein we report the path regeneration of a burnt?bridges DNA catenane walker using RNase?A. This walker uses a T7RNA polymerase that produces long RNA transcripts to hybridize to the path and move forward while the RNA remains hybridized to the path and blocks it for an additional walking cycle. We show that RNA degradation triggered by RNase?A restores the path and returns the walker to the initial position. RNase inhibition restarts the function of the walker. Making burnt bridges passable: A burnt?bridges DNA walker that employs long RNA transcripts for moving along steps on a DNA?nanotube path, can operate continuously when an enzymatic strategy is employed which consists of degrading the RNA that block the path through addition of RNase?A and subsequently restarting the walking through the use of an RNA inhibitor.

SUBMITTER: Valero J

PROVIDER: S-EPMC7540537 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

DNA Walker-Regulated Cancer Cell Growth Inhibition.

Project description:We demonstrate a DNAzyme-based walker system as a controlled oligonucleotide drug AS1411 release platform for breast cancer treatment. In this system, AS1411 strands are released from fuel strands as a walker moves along its carbon nanotube track. The release rate and amount of anticancer oligonucleotides are controlled by the walker operation. With a walker system embedded within the collagen extracellular matrix, we show that this drug release system can be used for in situ cancer cell growth inhibition.

| S-EPMC5051347 | biostudies-literature

Spinal Progenitor-Laden Bridges Support Earlier Axon Regeneration Following Spinal Cord Injury.

Project description:Impact statementSpinal cord injury (SCI) results in loss of tissue innervation below the injury. Spinal progenitors have a greater ability to repair the damage and can be injected into the injury, but their regenerative potential is hampered by their poor survival after transplantation. Biomaterials can create a cell delivery platform and generate a more hospitable microenvironment for the progenitors within the injury. In this work, polymeric bridges are used to deliver embryonic spinal progenitors to the injury, resulting in increased progenitor survival and subsequent regeneration and functional recovery, thus demonstrating the importance of combined therapeutic approaches for SCI.

| S-EPMC6238608 | biostudies-literature

A human XRCC4-XLF complex bridges DNA.

Project description:DNA double-strand breaks pose a significant threat to cell survival and must be repaired. In higher eukaryotes, such damage is repaired efficiently by non-homologous end joining (NHEJ). Within this pathway, XRCC4 and XLF fulfill key roles required for end joining. Using DNA-binding and -bridging assays, combined with direct visualization, we present evidence for how XRCC4-XLF complexes robustly bridge DNA molecules. This unanticipated, DNA Ligase IV-independent bridging activity by XRCC4-XLF suggests an early role for this complex during end joining, in addition to its more well-established later functions. Mutational analysis of the XRCC4-XLF C-terminal tail regions further identifies specialized functions in complex formation and interaction with DNA and DNA Ligase IV. Based on these data and the crystal structure of an extended protein filament of XRCC4-XLF at 3.94 Å, a model for XRCC4-XLF complex function in NHEJ is presented.

| S-EPMC3287209 | biostudies-literature

Self-Assembly of [3]Catenane and [4]Catenane Based on Neutral Organometallic Scaffolds.

Project description:Transition metal-mediated templating and self-assembly have shown great potential to construct mechanically interlocked molecules. Herein, we describe the formation of the bimetallic [3]catenane and [4]catenane based on neutral organometallic scaffolds via the orthogonality of platinum-to-oxygen coordination-driven self-assembly and copper(I) template-directed strategy of a [2]pseudorotaxane. The structures of these bimetallic [3]catenane and [4]catenane were characterized by multinuclear NMR {1H and 31P} spectroscopy, electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), and PM6 semiempirical molecular orbital theoretical calculations. In addition, single-crystal X-ray analyses of the [3]catenane revealed two asymmetric [2]pseudorotaxane units inside the metallacycle. It was discovered that tubular structures were formed through the stacking of individual [3]catenane molecules driven by the strong π-π interactions.

| S-EPMC8710481 | biostudies-literature

A stochastic DNA walker that traverses a microparticle surface.

Project description:Molecular machines have previously been designed that are propelled by DNAzymes, protein enzymes and strand displacement. These engineered machines typically move along precisely defined one- and two-dimensional tracks. Here, we report a DNA walker that uses hybridization to drive walking on DNA-coated microparticle surfaces. Through purely DNA:DNA hybridization reactions, the nanoscale movements of the walker can lead to the generation of a single-stranded product and the subsequent immobilization of fluorescent labels on the microparticle surface. This suggests that the system could be of use in analytical and diagnostic applications, similar to how strand exchange reactions in solution have been used for transducing and quantifying signals from isothermal molecular amplification assays. The walking behaviour is robust and the walker can take more than 30 continuous steps. The traversal of an unprogrammed, inhomogeneous surface is also due entirely to autonomous decisions made by the walker, behaviour analogous to amorphous chemical reaction network computations, which have been shown to lead to pattern formation.

| S-EPMC4740228 | biostudies-literature

Target-fueled DNA walker for highly selective miRNA detection.

Project description:Artificial DNA motifs as architectural scaffolds have been widely used to assemble a variety of nanoscale devices. Synthetic DNA nanostructures have accomplished mechanical switching in response to external stimuli, suggesting the promise of constructing a walking device that is being used in the field of biosensors. Here, we design a novel miRNA-responsive DNA walker biosensor based on strand displacement cascades and an enzymatic recycling cleavage strategy. By using miRNA as a driving force, the DNA walkers can be activated to move along the track and generate specific signals for let-7a with a high signal-to-noise ratio. This biosensor exhibits excellent analytical performance toward the sensing of let-7a with great specificity for resolving one nucleotide variation and a detection limit of 58 fM. Such an ultraselective sensor shows that DNA nanostructures have great potential in providing platforms for applications in the fields of biosensing, clinical diagnostics and environmental sample analysis.

| S-EPMC5508657 | biostudies-literature

Coupling across a DNA helical turn yields a hybrid DNA/organic catenane doubly tailed with functional termini.

Project description:We describe the synthesis of a hybrid DNA/organic macrocycle that is prepared by formation of an amide linkage across one full turn of DNA. Formation of a catenane proved that the linkage crossed a turn rather than running along the phosphodiester backbone contour. The product, a doubly tailed catenane, contains 5'- and 3'-termini that can be functionalized further or used to incorporate the catenane structure into other DNA assemblies.

| S-EPMC2712227 | biostudies-literature

Multifunctional, multichannel bridges that deliver neurotrophin encoding lentivirus for regeneration following spinal cord injury.

Project description:Therapeutic strategies following spinal cord injury must address the multiple barriers that limit regeneration. Multiple channel bridges have been developed that stabilize the injury following implantation and provide physical guidance for regenerating axons. These bridges have now been employed as a vehicle for localized delivery of lentivirus. Implantation of lentivirus loaded multiple channel bridges produced transgene expression that persisted for at least 4 weeks. Expression was maximal at the implant at the earliest time point, and decreased with increasing time of implantation, as well as rostral and caudal to the bridge. Immunohistochemical staining indicated transduction of macrophages, Schwann cells, fibroblasts, and astrocytes within the bridge and adjacent tissue. Subsequently, the delivery of lentivirus encoding the neurotrophic factors NT-3 or BDNF significantly increased the extent of axonal growth into the bridge relative to empty scaffolds. In addition to promoting axon growth, the induced expression of neurotrophic factors led to myelination of axons within the channels of the bridge, where the number of myelinated axons was significantly enhanced relative to control. Combining gene delivery with biomaterials to provide physical guidance and create a permissive environment can provide a platform to enhance axonal growth and promote regeneration.

| S-EPMC3237872 | biostudies-literature

An interparticle relatively motional DNA walker and its sensing application.

Project description:DNA molecular machines are DNA self-assemblies that perform quasi-mechanical movement at the micro-nano scale, and have attracted increasing attention in the fields of biosensing, drug delivery and biocomputing. Herein, we report the concept and operation of an interparticle relatively motional DNA walker. The walker is composed of walking particles (WPs) and track particles (TPs). The WPs and TPs are obtained by respective functionalization of locked walking strands containing DNAzyme sequences and fluorophore-labelled track strands containing substrate sequences onto gold nanoparticles (AuNPs). Triggered by the target that specifically unlocks the walking strand, the liberated walking strands cooperatively hybridize with the track strands. The track strand gets cleaved by the DNAzyme, accompanied by the fluorophore release. The adjacent walking strand on the WP subsequently hybridizes to the next track strand, inducing the relative motion of the WP around the TP. After walking along the surface of one TP, the WP can continue to interact with another TP. As a result of the improved moving freedom and area, the interparticle motional mode induces high continuity and achieves large signal accumulation. Taking Zika virus RNA fragments (ZIKV-RNA) as a model target, the DNA walker shows a high sensitivity with a detection limit of 118 pM, and can reliably detect the target in biological fluids due to the stability of its components. The constructed DNA walker provides a new type of free and robust motion mode between particles and holds potential in clinical diagnosis.

| S-EPMC8159414 | biostudies-literature

Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining.

Project description:Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with this activity, LigIII acts in an alternative pathway of DNA double strand break repair that buttresses canonical non-homologous end joining (NHEJ) and is manifest in NHEJ-defective cancer cells, but how LigIII acts in joining intermolecular DNA ends versus nick ligation is unclear. To investigate how LigIII efficiently joins two DNAs, we developed a real-time, fluorescence-based assay of DNA bridging suitable for high-throughput screening. On a nicked duplex DNA substrate, the results reveal binding competition between the ZnF and the oligonucleotide/oligosaccharide-binding domain, one of three domains constituting the LigIII catalytic core. In contrast, these domains collaborate and are essential for formation of a DNA-bridging intermediate by adenylated LigIII that positions a pair of blunt-ended duplex DNAs for efficient and specific intermolecular ligation.

| S-EPMC4538836 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data