scholarly journals pH-Responsive DNA Motif: From Rational Design to Analytical Applications

2021 ◽  
Vol 9 ◽  
Author(s):  
Lin Lin Zheng ◽  
Jin Ze Li ◽  
Ying Xu Li ◽  
Jian Bang Gao ◽  
Jiang Xue Dong ◽  
...  
Keyword(s):  
Base Pair ◽  
Rational Design ◽  
Secondary Structures ◽  
Triplex Dna ◽  
Ph Responsive ◽  
Dna Motifs ◽  
Response Properties ◽  
Ph Response ◽  
Dna Motif ◽  
Dna Secondary Structures

pH-responsive DNA motifs have attracted substantial attention attributed to their high designability and versatility of DNA chemistry. Such DNA motifs typically exploit DNA secondary structures that exhibit pH response properties because of the presence of specific protonation sites. In this review, we briefly summarized second structure-based pH-responsive DNA motifs, including triplex DNA, i-motif, and A+-C mismatch base pair-based DNA devices. Finally, the challenges and prospects of pH-responsive DNA motifs are also discussed.

scholarly journals Rational Design of pH‐Responsive DNA Motifs with General Sequence Compatibility

2019 ◽  
Vol 131 (46) ◽  
pp. 16557-16562 ◽  
Author(s):  
Wenhao Fu ◽  
Linlin Tang ◽  
Gaohui Wei ◽  
Liang Fang ◽  
Jie Zeng ◽  
...  
Keyword(s):  
Rational Design ◽  
Ph Responsive ◽  
General Sequence ◽  
Dna Motifs

scholarly journals Rational Design of Aptamer Switches with Programmable pH Response

2020 ◽  
Author(s):  
Ian A.P. Thompson ◽  
Liwei Zheng ◽  
Michael Eisenstein ◽  
H. Tom Soh
Keyword(s):  
Rational Design ◽  
Molecular Devices ◽  
Design Strategies ◽  
Ph Response ◽  
Dna Motif ◽  
Alkaline Conditions ◽  
Previous Design ◽  
Ph Conditions ◽  
Target Binding ◽  
Ph Range

AbstractAptamer switches that respond sensitively to local variations in pH could enable the development of molecular devices that greatly enhance diagnostic accuracy and therapeutic efficacy. Previous design strategies relied on inserting a known pH-sensitive DNA motif into the aptamer structure. Unfortunately, their performance was ultimately governed by the intrinsic pH-response of the inserted motif and could not be readily tuned to operate across arbitrary pH ranges. In this work, we present a general methodology for converting virtually any aptamer into a pH-responsive switch that can be modulated to undergo a strong change in affinity - in acidic, neutral, or alkaline conditions. This was achieved by inserting two orthogonal motifs that can be manipulated in parallel to tune sensitivity to different pH conditions without altering the core sequence of the aptamer itself. Using a single ATP aptamer, we achieve pH-dependent target binding and release under diverse pH conditions, producing as much as 1,000-fold pH-induced change in affinity. Importantly, we also demonstrate the novel capability to predictably engineer aptamer switches that only exhibit strong target affinity within a narrowly defined pH range. Our approach should offer a highly generalizable strategy for integrating pH-responsiveness into molecular devices.

scholarly journals Rational Design of pH‐Responsive DNA Motifs with General Sequence Compatibility

2019 ◽  
Vol 58 (46) ◽  
pp. 16405-16410 ◽  
Author(s):  
Wenhao Fu ◽  
Linlin Tang ◽  
Gaohui Wei ◽  
Liang Fang ◽  
Jie Zeng ◽  
...  
Keyword(s):  
Rational Design ◽  
Ph Responsive ◽  
General Sequence ◽  
Dna Motifs

scholarly journals CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giovanni Scala ◽  
Antonio Federico ◽  
Dario Greco
Keyword(s):  
Dna Methylation ◽  
Motif Discovery ◽  
Cpg Methylation ◽  
Functional Interpretation ◽  
Dna Motifs ◽  
Molecular Alterations ◽  
Link Type ◽  
Dna Motif ◽  
Quantitative Manner ◽  
Dna Motif Discovery

Abstract Background The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.

scholarly journals DNA secondary structures are associated with recombination in major Plasmodium falciparum variable surface antigen gene families

2013 ◽  
Vol 42 (4) ◽  
pp. 2270-2281 ◽  
Author(s):  
Adam F. Sander ◽  
Thomas Lavstsen ◽  
Thomas S. Rask ◽  
Michael Lisby ◽  
Ali Salanti ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Protein ◽  
Erythrocyte Membrane ◽  
Gene Families ◽  
Secondary Structures ◽  
Erythrocyte Membrane Protein ◽  
Sexual Stages ◽  
Dna Secondary Structures ◽  
Parasitic Pathogens ◽  
Falciparum Erythrocyte Membrane Protein

Abstract Many bacterial, viral and parasitic pathogens undergo antigenic variation to counter host immune defense mechanisms. In Plasmodium falciparum, the most lethal of human malaria parasites, switching of var gene expression results in alternating expression of the adhesion proteins of the Plasmodium falciparum-erythrocyte membrane protein 1 class on the infected erythrocyte surface. Recombination clearly generates var diversity, but the nature and control of the genetic exchanges involved remain unclear. By experimental and bioinformatic identification of recombination events and genome-wide recombination hotspots in var genes, we show that during the parasite’s sexual stages, ectopic recombination between isogenous var paralogs occurs near low folding free energy DNA 50-mers and that these sequences are heavily concentrated at the boundaries of regions encoding individual Plasmodium falciparum-erythrocyte membrane protein 1 structural domains. The recombinogenic potential of these 50-mers is not parasite-specific because these sequences also induce recombination when transferred to the yeast Saccharomyces cerevisiae. Genetic cross data suggest that DNA secondary structures (DSS) act as inducers of recombination during DNA replication in P. falciparum sexual stages, and that these DSS-regulated genetic exchanges generate functional and diverse P. falciparum adhesion antigens. DSS-induced recombination may represent a common mechanism for optimizing the evolvability of virulence gene families in pathogens.

scholarly journals Pif1 is essential for efficient replisome progression through lagging strand G-quadruplex DNA secondary structures

2018 ◽  
Vol 46 (22) ◽  
pp. 11847-11857 ◽  
Author(s):  
Danielle Dahan ◽  
Ioannis Tsirkas ◽  
Daniel Dovrat ◽  
Melanie A Sparks ◽  
Saurabh P Singh ◽  
...  
Keyword(s):  
Secondary Structures ◽  
Quadruplex Dna ◽  
G Quadruplex ◽  
Dna Secondary Structures ◽  
Lagging Strand

scholarly journals Non-B DNA Secondary Structures and Their Resolution by RecQ Helicases

2011 ◽  
Vol 2011 ◽  
pp. 1-15 ◽  
Author(s):  
Sudha Sharma
Keyword(s):  
Transcriptional Control ◽  
Molecular Targets ◽  
Secondary Structures ◽  
Special Focus ◽  
Dna Helicases ◽  
Dna Structures ◽  
Recq Helicases ◽  
Alternative Structures ◽  
Dna Secondary Structures ◽  
Secondary Dna Structures

In addition to the canonical B-form structure first described by Watson and Crick, DNA can adopt a number of alternative structures. These non-B-form DNA secondary structures form spontaneously on tracts of repeat sequences that are abundant in genomes. In addition, structured forms of DNA with intrastrand pairing may arise on single-stranded DNA produced transiently during various cellular processes. Such secondary structures have a range of biological functions but also induce genetic instability. Increasing evidence suggests that genomic instabilities induced by non-B DNA secondary structures result in predisposition to diseases. Secondary DNA structures also represent a new class of molecular targets for DNA-interactive compounds that might be useful for targeting telomeres and transcriptional control. The equilibrium between the duplex DNA and formation of multistranded non-B-form structures is partly dependent upon the helicases that unwind (resolve) these alternate DNA structures. With special focus on tetraplex, triplex, and cruciform, this paper summarizes the incidence of non-B DNA structures and their association with genomic instability and emphasizes the roles of RecQ-like DNA helicases in genome maintenance by resolution of DNA secondary structures. In future, RecQ helicases are anticipated to be additional molecular targets for cancer chemotherapeutics.

Stabilised DNA secondary structures with increasing transcription localise hypermutable bases for somatic hypermutation in IGHV3-23

2012 ◽  
Vol 64 (7) ◽  
pp. 481-496 ◽  
Author(s):  
Bhargavi Duvvuri ◽  
Venkata R. Duvvuri ◽  
Jianhong Wu ◽  
Gillian E. Wu
Keyword(s):  
Somatic Hypermutation ◽  
Secondary Structures ◽  
Dna Secondary Structures

scholarly journals Engineering DNA recognition and allosteric response properties of TetR family proteins by using a module-swapping strategy

2019 ◽  
Vol 47 (16) ◽  
pp. 8913-8925 ◽  
Author(s):  
Rey P Dimas ◽  
Benjamin R Jordan ◽  
Xian-Li Jiang ◽  
Catherine Martini ◽  
Joseph S Glavy ◽  
...  
Keyword(s):  
Dna Binding ◽  
Ligand Binding ◽  
Cellular Response ◽  
Rational Design ◽  
Dna Recognition ◽  
Response Properties ◽  
Effective Components ◽  
Uniprot Accession ◽  
Engineering Strategy ◽  
Molecular Signal

Abstract The development of synthetic biological systems requires modular biomolecular components to flexibly alter response pathways. In previous studies, we have established a module-swapping design principle to engineer allosteric response and DNA recognition properties among regulators in the LacI family, in which the engineered regulators served as effective components for implementing new cellular behavior. Here we introduced this protein engineering strategy to two regulators in the TetR family: TetR (UniProt Accession ID: P04483) and MphR (Q9EVJ6). The TetR DNA-binding module and the MphR ligand-binding module were used to create the TetR-MphR. This resulting hybrid regulator possesses DNA-binding properties of TetR and ligand response properties of MphR, which is able to control gene expression in response to a molecular signal in cells. Furthermore, we studied molecular interactions between the TetR DNA-binding module and MphR ligand-binding module by using mutant analysis. Together, we demonstrated that TetR family regulators contain discrete and functional modules that can be used to build biological components with novel properties. This work highlights the utility of rational design as a means of creating modular parts for cell engineering and introduces new possibilities in rewiring cellular response pathways.

scholarly journals Development of a pH-responsive polymersome inducing endoplasmic reticulum stress and autophagy blockade

2020 ◽  
Vol 6 (31) ◽  
pp. eabb8725 ◽  
Author(s):  
Funeng Xu ◽  
Xilin Li ◽  
Xuehui Huang ◽  
Jingmei Pan ◽  
Yi Wang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Tumor Metastasis ◽  
Focal Adhesions ◽  
Matrix Metalloproteinase 2 ◽  
Autophagic Flux ◽  
Ph Responsive ◽  
Ph Response ◽  
Function Mechanism ◽  
Inhibit Tumor Metastasis

Autophagy is involved in the occurrence and development of tumors. Here, a pH-responsive polymersome codelivering hydroxychloroquine (HCQ) and tunicamycin (Tuni) drugs is developed to simultaneously induce endoplasmic reticulum (ER) stress and autophagic flux blockade for achieving an antitumor effect and inhibiting tumor metastasis. The pH response of poly(β-amino ester) and HCQ synergistically deacidifies the lysosomes, thereby blocking the fusion of autophagosomes and lysosomes and lastly blocking autophagic flux. The function mechanism of regulating autophagy was systematically investigated on orthotopic luciferase gene–transfected, 4T1 tumor–bearing BALB/c mice through Western blot and immunohistochemistry analyses. The Tuni triggers ER stress to regulate the PERK/Akt signaling pathway to increase the autophagic level. The “autophagic stress” generated by triggering ER stress–induced autophagy and blocking autophagic flux is effective against tumors. The reduced expression of matrix metalloproteinase-2 due to ER stress and reduced focal adhesions turnover due to the blockade of autophagic flux synergistically inhibit tumor metastasis.

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