DNA articles within Nature Chemistry

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  • Research Briefing |

    Nanomachines are central to life and are becoming an important part of self-regulated nanotechnologies. Inspired by natural self-assembled nanosystems, it has been shown that artificial nanosystems can evolve and adopt regulatory functions upon fragmentation of their structures into multiple components that reassemble to form the same nanostructure.

  • Article |

    Combinatorial high-throughput methodologies can accelerate screening and discovery in biochemistry and biomedical sciences, but they often rely on large-scale analyses, making them time-consuming and expensive. Now, DNA-mediated fusion of single liposomes has been shown to enable the spatially resolved and parallel cargo delivery of subattolitre volumes in a stochastic order of succession.

    • Mette Galsgaard Malle
    • , Philipp M. G. Löffler
    •  & Nikos S. Hatzakis

  • Perspective |

    DNA-encoded libraries can be applied in a diverse range of applications beyond simple binding assays. This Perspective covers the recent progress in using DNA-encoded chemical libraries to investigate complex biological targets and discusses their potential to identify structures that elicit function or possess other useful properties.

    • Yiran Huang
    • , Yizhou Li
    •  & Xiaoyu Li

  • News & Views |

    Nucleic acids can adopt G-quadruplex folds whose cellular roles remain poorly defined. Synthesis of new probes has now enabled the identification of human proteins that interact with G-quadruplexes. This could provide new clues to decipher the function of these curious folds.

    • Aaron M. Fleming
    •  & Cynthia J. Burrows

  • News & Views |

    DNA-encoded libraries are a powerful tool to identify hit compounds for drug discovery. Now, two papers have reported new advances in this technology. One paper reports a method to screen for binders inside a living cell, and the other investigates the effects of stereo- and regiochemistry on ligand discovery.

    • Minsoo Song
    •  & Gil Tae Hwang

  • Article |

    DNA G-quadruplexes can adopt a variety of secondary structures, but it is challenging to identify and classify them quickly. Multivariate analysis of different fluorescence enhancements—generated from an arrayed suite of synthetic hosts and cationic dyes—enables discrimination between G-quadruplex structures of identical length and similar topological types.

    • Junyi Chen
    • , Briana L. Hickey
    •  & Wenwan Zhong

  • News & Views |

    The therapeutic applications of DNAzymes are limited because of their low effectiveness in vivo. Now, a promising approach for constructing DNAzymes that show high gene-silencing efficiency in mammalian cells has been developed. This approach incorporates chemical modifications into an existing DNAzyme scaffold.

    • Yifei Zhou
    •  & Chuanzheng Zhou

  • Article |

    A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells.

    • Yiran Huang
    • , Ling Meng
    •  & Xiaoyu Li

  • News & Views |

    Tailor-made reverse transcriptases are used in molecular biology and synthetic genetics. However, re-engineering these enzymes to work with non-natural nucleic acids is difficult and requires powerful directed evolution strategies. Now, an adaptable selection approach has been demonstrated for the evolution of new reverse transcriptases.

    • Melanie Henkel
    •  & Andreas Marx

  • Article |

    Visualization of endogenous G-quadruplexes (G4s) in living cells by fluorescence microscopy has been hampered by the high concentrations of G4-binding probes required, which can artificially induce additional G4 formation. Now, a G4-specific fluorescent probe (SiR-PyPDS) has been developed that enables single-molecule and real-time detection of individual G4 structures in living cells without perturbing G4 formation and dynamics.

    • Marco Di Antonio
    • , Aleks Ponjavic
    •  & Shankar Balasubramanian

  • Article |

    The emergence of pristine RNA and DNA on the early Earth would have been hindered by a lack of specificity in their prebiotic syntheses. Now, it has been shown that chimeric sequences—with a mixture of RNA and DNA backbones—mediate the template-directed ligation of oligomers present in mixtures of nucleic acids, enabling the simultaneous appearance of RNA and DNA.

    • Subhendu Bhowmik
    •  & Ramanarayanan Krishnamurthy

  • Article |

    Abasic sites are amongst the most common forms of DNA damage. Despite their biological significance, little is known regarding the distribution of these sites within DNA. Now a method to sequence abasic sites at single-nucleotide resolution has been developed. This method allows the location of abasic sites to be mapped genome-wide.

    • Zheng J. Liu
    • , Sergio Martínez Cuesta
    •  & Shankar Balasubramanian

  • Article |

    I-motif DNA structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Now an engineered antibody that is selective for i-motif structures has been developed and used to detect i-motifs in the nuclei of human cells.

    • Mahdi Zeraati
    • , David B. Langley
    •  & Daniel Christ

  • Article |

    The rate constant of DNA hybridization varies over several orders of magnitude and is affected by temperature and DNA sequence. A machine-learning algorithm that is capable of accurately predicting hybridization rate constants has now been developed. Tests with this algorithm showed that over 90% of predictions were correct to within a factor of three.

    • Jinny X. Zhang
    • , John Z. Fang
    •  & David Yu Zhang

  • News & Views |

    Understanding the biological roles of modifications to DNA, RNA and proteins is critical to revealing how cells regulate gene expression in development and disease. Two papers now present a combination of new tools and discoveries that could enable biologists and chemical biologists to better study epigenetic regulation in mammals.

    • Bryan T. Harada
    •  & Chuan He

  • Article |

    A 335 base-pair gene encoding the green fluorescent protein iLOV and an epigenetically modified variant have now been assembled by click-DNA ligation of ten functionalized oligonucleotides. The resulting fully synthetic gene contained eight triazoles at the sites of chemical ligation, yet the synthetic gene was shown to be fully biocompatible in Escherichia coli.

    • Mikiembo Kukwikila
    • , Nittaya Gale
    •  & Ali Tavassoli

  • News & Views |

    A quantitative understanding of the functional landscape of a biochemical circuit can reveal the design rules required to optimize the circuit. Now, a high-throughput droplet-based microfluidic platform has been developed which enables high-resolution mapping of bifurcation diagrams for two nonlinear DNA networks.

    • Fei Wang
    •  & Chunhai Fan

  • Article |

    Dynamic nonlinear biochemical circuits are functionally rich; however, this nonlinear nature also makes programming them delicate and painstaking. Now a droplet microfluidic platform reveals precisely the bifurcations of two canonical systems: a bistable switch and a predator–prey oscillator, exposing optimal regions and mechanistic insights that inform the design of these systems.

    • A. J. Genot
    • , A. Baccouche
    •  & Y. Rondelez

  • News & Views |

    A pair of artificial DNA bases have now been shown to adopt an edge-to-edge geometry in DNA which is similar that found in Watson–Crick base pairing. Aptamers containing these bases have also been shown to bind more strongly to a target than those developed using only the four naturally occurring bases.

    • Cheulhee Jung
    •  & Andrew D. Ellington

  • Article |

    The use of kinetic simulations to guide the design of competitive hybridization probe systems is shown to enable high selectivity for single-nucleotide variants. Using this approach across 44 cancer mutation/wild-type sequence pairs showed between a 200- and 3,000-fold higher binding affinity than the corresponding wild-type sequence. In combination with PCR amplification this method enabled the detection of a 1% concentration of variant alleles in human genomic DNA.

    • Juexiao Sherry Wang
    •  & David Yu Zhang

  • Article |

    Charge transport in molecular systems is typically through coherent tunnelling over a short distance or incoherent hopping over a long distance. An intermediate regime between those two transport mechanisms has now been found for DNA systems with stacked guanine–cytosine sequences.

    • Limin Xiang
    • , Julio L. Palma
    •  & Nongjian Tao

  • News & Views |

    DNA self-assembly has previously been used to create channel-like structures that can penetrate through lipid bilayer membranes. However, such assemblies have not been shown to cause cell death before. Now a DNA nanopore has been shown to exert a cytotoxic effect when administered to cells.

    • Swati Krishnan
    •  & Friedrich C. Simmel

  • News & Views |

    Oxidation of 5-methylcytosine has been proposed to mediate active and passive DNA demethylation. Tracking the history of DNA modifications has now provided the first solid evidence that 5-hydroxymethylcytosine is a stable epigenetic modification.

    • Pijus Brazauskas
    •  & Skirmantas Kriaucionis

  • Article |

    Recognition, differentiation and sensing of small molecules displaying only sparse functionalities using artificial receptors is extremely challenging. Now a method to selectively bind and recognise low-epitope targets has been developed. The approach uses the formation of ternary complexes between small-molecule targets, their non-specific organic (or organometallic) receptors, and aptamers.

    • Kyung-Ae Yang
    • , Mihaela Barbu
    •  & Milan N. Stojanovic

  • Article |

    Reduction of 5-hydroxymethylcytosine (hmC) levels in DNA often occurs in cancers. Using isotope tracing experiments, this epigenetic DNA modification, which was thought to be an intermediate of demethylation, is now shown to be stable. A delay in the generation of hmC on newly synthesized DNA is responsible for the reduction of hmC levels in cancers.

    • Martin Bachman
    • , Santiago Uribe-Lewis
    •  & Shankar Balasubramanian

  • News & Views |

    The lomaiviticins are exceedingly potent antibiotic agents, but the mechanism responsible for this activity has so far been unclear. Now, efficient generation of double-strand breaks in DNA by lomaiviticin A has been linked to the remarkable cytotoxicity of these diazobenzofluorene-containg natural products.

    • Kent S. Gates

  • Article |

    Cytosine base modifications 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) are present in mammalian DNA. Reduced bisulfite sequencing is now developed for quantitatively sequencing 5fC at single-base resolution. This method is then applied with oxidative bisulfite sequencing to gain a map of 5mC, 5hmC and 5fC in mouse embryonic stem cells.

    • Michael J. Booth
    • , Giovanni Marsico
    •  & Shankar Balasubramanian

  • News & Views |

    Strategies for making sequence-controlled polymers in the laboratory are really quite primitive in comparison with those used in nature. By combining concepts from natural systems and synthetic polymer chemistry, it has now been shown that DNA codes can be translated into non-nucleic-acid polymers with defined sequences.

    • Rachel K. O'Reilly

  • Article |

    An enzyme-free system that translates DNA into sequence-defined non-nucleic acid polymers including polyethylene glycol, α-(D)-peptides and β-peptides is described. Sequence-defined polymers with molecular weights of 26 kDa containing 16 consecutively coupled building blocks and 90 densely functionalized β-amino acids were translated from DNA templates using this strategy.

    • Jia Niu
    • , Ryan Hili
    •  & David R. Liu

  • News & Views |

    The direct observation and quantification of G-quadruplex structures formed from DNA in human cells during the cell cycle demonstrate the biological importance of these structures and point towards opportunities for targeting them with small-molecule drugs.

    • Adam Siddiqui-Jain
    •  & Laurence H. Hurley

  • News & Views |

    A tetra-intercalator compound that threads through a DNA double-helix to form a remarkably stable complex exhibits an unusual combination of sequence specificity and rapid association yet slow dissociation.

    • Adam R. Urbach

  • Article |

    Molecules that bind to DNA for extended periods can modulate its transcription or other biological processes. Kinetic studies on the non-covalent complex formed by a threading tetra-intercalator and a DNA double-helix have now revealed a multi-step association, and a particularly slow dissociation leading to sequence specificity and a 16-day half-life.

    • Garen G. Holman
    • , Maha Zewail-Foote
    •  & Brent L. Iverson

  • Article |

    The potential for using molecules as wires in nanoscale electronics is somewhat tempered by the challenges in making long and uniform structures. Now, it has been shown that DNA — which is easily synthesized to precise lengths — can conduct charge over 34 nm on multiplexed gold electrodes, a distance that surpasses most reports of molecular wires.

    • Jason D. Slinker
    • , Natalie B. Muren
    •  & Jacqueline K. Barton

  • Article |

    The assembly and evaluation of molecular structures on surfaces has been boosted by advances in single-molecule techniques. The development of such methods are continued here, showing that double-stranded DNA, bound to the tip of an atomic force microscope, can be deposited on the surface of a gold electrode using an electrical trigger.

    • Matthias Erdmann
    • , Ralf David
    •  & Hermann E. Gaub

  • Article |

    The incorporation of non-natural base pairs into double-stranded DNA, especially those mediated by metal–ligand interactions, offers new opportunities for synthetic DNA materials. The structural implications of such modifications will help guide developments in this area, and a solution structure of a B-type DNA duplex containing consecutive metal-mediated base pairs has now been elucidated.

    • Silke Johannsen
    • , Nicole Megger
    •  & Jens Müller

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