A5038643917- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Molecular Junctions and Nanostructures
- Force Microscopy Techniques and Applications
- Genomics and Chromatin Dynamics
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Groundwater flow and contamination studies
- Pluripotent Stem Cells Research
- Carbon and Quantum Dots Applications
- Hydraulic Fracturing and Reservoir Analysis
- Graphene and Nanomaterials Applications
- Dam Engineering and Safety
- Heavy Metal Exposure and Toxicity
- Cancer-related molecular mechanisms research
- Extracellular vesicles in disease
- ICT in Developing Communities
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- Microfluidic and Bio-sensing Technologies
Nankai University
2019-2025
State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering
2011-2020
Hohai University
2020
Delft University of Technology
2014-2016
Kent State University
2009-2015
Significance RNA, like DNA, can form double helices held together by the pairing of complementary bases, and such are ubiquitous in functional RNAs. Here we apply external forces torques to individual double-stranded RNA molecules determine mechanical properties conformational transitions these fundamental biological building blocks. For small torques, behave elastic rods, have determined their bending, stretching, twisting stiffness. Surprisingly, find that shortens when it is overwound,...
Intramolecular folding in three tandem guanine repeats of human telomeric DNA has been investigated using optical-tweezers, MD simulation and circular dichroism. A mechanically thermodynamically stable species this sequence shows a structure consistent with triplex conformation. similar also observed to coexist G-quadruplex four repeats.
The insulin linked polymorphism region (ILPR) is known to regulate transcription of the gene coding for insulin. ILPR has guanine rich segments, suggesting that G quadruplexes may be responsible this regulatory role. Using mechanical unfolding in a laser tweezers instrument and circular dichroism (CD) spectroscopy, we provide compelling evidence highly stable parallel antiparallel quadruplex structures coexist predominant sequence (ACAGGGGTGTGGGG)2 at physiologically relevant concentration...
Investigation of i-motif is high importance to fully understand the biological functions G quadruplexes in context double-stranded DNA. Whereas single-molecule approaches have profiled from a perspective unavailable by bulk techniques, there lack similar literature on cytosine (C)-rich region complementary quadruplex-forming sequences. Here, we used laser tweezers investigate structures formed 5′-(TGTCCCCACACCCC)2, predominate variant insulin-linked polymorphic (ILPR). We observed two...
Recent experiments provided controversial observations that either parallel or non-parallel G-quadruplex exists in molecularly crowded buffers mimic cellular environment. Here, we used laser tweezers to mechanically unfold structures a human telomeric DNA fragment, 5′-(TTAGGG)4TTA, along three different trajectories. After the end-to-end distance of each unfolding geometry was measured, it compared with PDB identify best-matching conformation. This method is well-suited biomolecular complex...
To study the behavior of biological macromolecules and enzymatic reactions under force, advances in single-molecule force spectroscopy have proven instrumental. Magnetic tweezers form one most powerful these techniques, due to their overall simplicity, non-invasive character, potential for high throughput measurements, large range. Drawbacks magnetic tweezers, however, are that accurate determination applied forces can be challenging short biomolecules at very time-consuming long tethers low...
The discovery of G-quadruplexes and other DNA secondary elements has increased the structural diversity well beyond ubiquitous double helix. However, it remains to be determined whether tertiary interactions can take place in a complex that contains more than one structure. Using new data analysis strategy exploits hysteresis region between mechanical unfolding refolding traces obtained by laser-tweezers instrument, we now provide first convincing kinetic thermodynamic evidence higher order...
It has been proposed that new transcription modulations can be achieved via topological coupling between duplex DNA and secondary structures, such as G-quadruplexes, in gene promoters through superhelicity effects. Limited by available methodologies, however, a not quantified directly. In this work, using novel magneto-optical tweezers combine the nanometer resolution of optical easy manipulation magnetic tweezers, we found flexibility increases with positive (σ). More interestingly,...
The well-demonstrated biological functions of DNA G-quadruplex inside cells call for small molecules that can modulate these activities by interacting with G-quadruplexes. However, the paucity understanding stability contributed from submolecular elements, such as loops and tetraguanine (G) planes (or G-quartets), has hindered development small-molecule binders. Assisted click chemistry, herein, we attached pulling handles via two modified guanines in each three G-quartets human telomeric...
Here we report the analysis of dual G-quadruplexes formed in four repeats consensus sequence from insulin-linked polymorphic region (ACAGGGGTGTGGGG; ILPRn=4). Mobilities ILPRn=4 nondenaturing gel and circular dichroism (CD) studies confirmed formation two intramolecular sequence. Both CD single molecule using optical tweezers showed that quadruplexes most likely adopt a hybrid G-quadruplex structure was entirely different mixture parallel antiparallel conformers previously observed forming...
Aptamers that bind small molecules can serve as basic biosensing platforms. Evaluation of the binding constant between an aptamer and a molecule helps to determine effectiveness aptamer-based sensors. Binding constants are often measured by series experiments with varying ligand or concentrations. Such time-consuming, material nonprudent, prone low reproducibility. Here, we use laser tweezers dissociation for aptamer-ligand interactions at single-molecule level from only one concentration....
Single nucleotide polymorphism (SNP) is the most common genetic variation among individuals. The association of SNP with individual's response to pathogens, phenotypic variations, and gene functions emphasizes importance sensitive reliable detection for biomedical diagnosis therapy. To increase sensitivity, approaches employ amplification steps, such as PCR, generate detectable signals that are usually ensemble-averaged. Introduction steps increases complexity a system, whereas ensemble...
Abstract With the firm demonstration of in vivo presence and biological functions many non‐ B DNA structures, it is great significance to understand their physiological roles from perspective structural conformation, stability, transition kinetics. Although relatively simple primary sequences compared proteins, species show rather versatile conformations dynamic transitions. As most‐studied species, G ‐quadruplex displays a myriad that can interconvert between each other different solutions....
Abstract The transformation from one compound to another involves the breaking and formation of chemical bonds at single-bond level, especially during catalytic reactions that are great significance in broad fields such as energy conversion, environmental science, life science synthesis. study reaction process limit is key understanding mechanism further rationally designing catalysts. Here, we develop a method monitor perspective using high-resolution scanning tunneling microscopy...
A 3D folding funnel was proposed in the 1990s to explain fast kinetics exhibited by a biomacromolecule presence of seemingly unlimited pathways. Over years, numerous simulations have been performed with this concept; however, experimental verification is yet be attained even for simplest proteins. Here, we used click chemistry based strategy introduce six pairs handles human telomeric DNA sequence. laser-tweezers-based, single-molecule structural fingerprinting on inter-handle distances...
Guanine-rich DNA sequences with short G-tracts (n ≤ 2) are highly prevalent and abundant in the human genome, some of which found to be associated diseases (Maity et al. Nucleic Acids Res. 2020, 48 (6), 3315-3327). Unlike conventional G-quadruplexes three or more folded layers, these G2 tracts featuring two bilayered blocks remain largely unexplored. Here, we employed nanopore experiments all-atom molecular dynamics simulations investigate unwinding strengths blocks. Our results demonstrated...
Enrichment of four tandem repeats guanine (G) rich and cytosine (C) sequences in functionally important regions human genome forebodes the biological implications four-stranded DNA structures, such as G-quadruplex i-motif, that can form these sequences. However, there have been few reports on intramolecular formation non-B structures less than G or C Here, using mechanical unfolding at single-molecule level, electrophoretic mobility shift assay (EMSA), circular dichroism (CD), ultraviolet...
Due to the long-range nature of high-order interactions between distal components in a biomolecule, transition dynamics tertiary structures is often too complex profile using conventional methods. Inspired by exploded view mechanical drawing, here, we used laser tweezers mechanically dissect DNA into two constituting G-quadruplexes promoter human telomerase reverse transcriptase (hTERT) gene. Assisted with click-chemistry coupling, sandwiched one G-quadruplex dsDNA handles while leaving...
A telomere carrying repetitive sequences ends with a single-stranded overhang. The G-rich overhang could fold back and bind in the major groove of its upstream duplex, forming an antiparallel triplex structure. telomeric has been proposed to function protecting chromosome ends. However, we lack strategies mechanically probe dynamics triplex. Here, show that topological involves 3' binding at ds/ssDNA junction inferred by DNA mechanics. Assisted click chemistry branched polymerase chain...