γ-Hemolysin Nanopore Is Sensitive to Guanine-to-Inosine Substitutions in Double-Stranded DNA at the Single-Molecule Level

Tan, Cherie S.; Fleming, Aaron M.; Ren, Haixia; Burrows, Cynthia J.; White, Henry S.

doi:10.1021/jacs.8b08153

Cited by 30 publications

(27 citation statements)

References 68 publications

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“…ellular and organelle membranes play pivotal roles in controlling and maintaining biological activities, including environmental sensing, energy conversion, signal transduction and substance transportation. A significant part of these functions is realized by a series of proteins so-called transmembrane proteins, and their structure-function relationships have been attracting interest not only in biology and medicine, but also in chemistry and materials science for developing functional molecules and nanodevices [1][2][3] . Inspired by the proteinic channels, for example, numerous types of synthetic supramolecular ion channels have been developed [4][5][6] , and ion transportation through biological membranes have been demonstrated 7,8 .…”

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confidence: 99%

A synthetic ion channel with anisotropic ligand response

et al. 2020

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Biological membranes play pivotal roles in the cellular activities. Transmembrane proteins are the central molecules that conduct membrane-mediated biochemical functions such as signal transduction and substance transportation. Not only the molecular functions but also the supramolecular properties of the transmembrane proteins such as self-assembly, delocalization, orientation and signal response are essential for controlling cellular activities. Here we report anisotropic ligand responses of a synthetic multipass transmembrane ion channel. An unsymmetrical molecular structure allows for oriented insertion of the synthetic amphiphile to a bilayer by addition to a pre-formed membrane. Complexation with a ligand prompts ion transportation by forming a supramolecular channel, and removal of the ligand deactivates the transportation function. Biomimetic regulation of the synthetic channel by agonistic and antagonistic ligands is also demonstrated not only in an artificial membrane but also in a biological membrane of a living cell.

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confidence: 99%

A synthetic ion channel with anisotropic ligand response

et al. 2020

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“…Burrows and colleagues pioneered the application of nanopore-type technology for sequencing DNA adducts in single-stranded DNA. With custom-made solid-state or proteinbased nanopores, they showed the proof-of-principle for detecting N 2 -BPDE-dG-induced adducts [60], abasic sites [61][62][63], and other DNA adducts [64], including 8-oxo-dG [65][66][67].…”

Section: Nanopore Technologymentioning

confidence: 99%

Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts

Boysen

Nookaew

2022

Toxics

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Formation of DNA adducts is a key event for a genotoxic mode of action, and their presence is often used as a surrogate for mutation and increased cancer risk. Interest in DNA adducts are twofold: first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. Methods have been established to quantitate DNA adducts with high chemical specificity and to visualize the location of DNA adducts, and elegant bio-analytical methods have been devised utilizing enzymes, various chemistries, and molecular biology methods. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. Herein, we briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technologies to achieve both measures. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation.

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“…Burrows and colleagues pioneered the application of nanopore-type technology for sequencing DNA adducts in single-stranded DNA. With custom-made solid-state or protein-based nanopores, they showed the proof-of-principle for detecting N 2 -BPDE-dG-induced adducts [56], abasic sites [57][58][59], and other DNA adducts [60], including 8-oxo-dG [61][62][63].…”

Section: Nanopore Technologymentioning

confidence: 99%

Current and Future Methodology for Quantitation and Site-specific Mapping the Location of DNA Adducts

Boysen¹,

Nookaew²

2021

Preprint

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Formation of DNA adducts is a key event for a genotoxic mode of action and its formation is often use as surrogate for mutation and cancer. Interest in DNA adducts are twofold, first, to demonstrate exposure, and second, to link DNA adduct location to subsequent mutations or altered gene regulation. High chemically specific mass spectrometry methods have been established for DNA adduct quantitation and elegant bio-analytic methods utilizing enzymes, various chemistries, and molecular biology methods to visualize the location of DNA adducts. Traditionally, these highly specific methods cannot be combined, and the results are incomparable. Initially developed for single-molecule DNA sequencing, nanopore-type technologies are expected to enable simultaneous quantitation and location of DNA adducts across the genome. We will briefly summarize the current methodologies for state-of-the-art quantitation of DNA adduct levels and mapping of DNA adducts and describe novel single-molecule DNA sequencing technology that is expected to achieve both measures simultaneously. Emerging technologies are expected to soon provide a comprehensive picture of the exposome and identify gene regions susceptible to DNA adduct formation.

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γ-Hemolysin Nanopore Is Sensitive to Guanine-to-Inosine Substitutions in Double-Stranded DNA at the Single-Molecule Level

Cited by 30 publications

References 68 publications

A synthetic ion channel with anisotropic ligand response

A synthetic ion channel with anisotropic ligand response

Current and Future Methodology for Quantitation and Site-Specific Mapping the Location of DNA Adducts

Current and Future Methodology for Quantitation and Site-specific Mapping the Location of DNA Adducts

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