Previous computational studies have shown that Cu+ can act as a substitute for H+ to support formation of cytosine (C) dimers with similar conformation to the hemi-protonated base pair found in i-motif DNA. Through a range of biophysical methods, we provide experimental evidence to support the hypothesis that Cu+ can mediate C-C base pairing in i-motif DNA and preserve i-motif structure. These effects can be reversed using a metal chelator, or exposure to ambient oxygen in the air that drives oxidation of Cu+ to Cu2+, a comparatively weak ligand. Herein, we present a dynamic and redox-sensitive system for conformational control of an i-motif forming DNA sequence in response to copper cations.
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http://dx.doi.org/10.1093/nar/gky390 | DOI Listing |
J Phys Chem Lett
January 2025
State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Research Center for Innovative Technology of Pharmaceutical Analysis, College of Pharmacy, Harbin Medical University, Heilongjiang 150081, PR China.
Surface-enhanced Raman spectroscopy (SERS) has become an indispensable tool for biomolecular analysis, yet the detection of DNA signals remains hindered by spectral interference from citrate ions, which overlap with key DNA features. This study introduces an innovative, ultrasensitive SERS platform utilizing thiol-modified silver nanoparticles (Ag@SDCNPs) that overcomes this challenge by eliminating citrate interference. This platform enables direct, interference-free detection and structural characterization of a wide range of DNA conformations, including single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), i-motif, hairpin, G-quadruplex, and triple-stranded DNA (tsDNA).
View Article and Find Full Text PDFChembiochem
January 2025
Peking University, College of Chemistry and Molecular Engineering, No. 292 Chengfu Road, Haidian District, 100871, Beijing, CHINA.
Since the building blocks of DNA are nonfluorescent, various external fluorescence reporters have been employed to investigate the structure, dynamics, and function of DNA G-quadruplexes (GQs) and i-motifs (iMs), which play an important role in gene regulation and expression. However, most of those fluorescence reporters lack the ability to provide site-specific structural information of interest. Therefore, it is necessary to develop fluorescent nucleoside analogues that can be covalently inserted into oligonucleotides, which not only serve this purpose, but minimize any potential perturbation towards the native structure of the DNA systems in question.
View Article and Find Full Text PDFBiol Lett
January 2025
Discovery, InsideOutBio , Charlestown, MA, USA.
This paper is focused on the origins of the contemporary genetic code. A novel explanation is proposed for how the mapping of nucleotides in DNA to amino acids in proteins arose that derives from repeat nucleotide sequences able to form alternative nucleic acid structures (ANS), such as the unusual left-handed Z-DNA, triplex, G-quadruplex and I-motif conformations. The scheme identifies sequence-specific contacts that map ANS repeats to dipeptide polymers (DPS).
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Chemistry, Yeungnam University, 280 Daehak-ro, Gyeongsan-si, Gyeongsangbuk-do 38541, Republic of Korea.
Recent studies have reported that the cause and progression of many diseases are closely related to complex and diverse gene regulation involving multiple microRNAs (miRNAs). However, most existing methods for miRNA detection typically deal with one sample at a time, which limits the achievement of high diagnostic accuracy for diseases associated with multiple gene dysregulations. Herein, we develop a liquid flow-based microfluidic optical assay for the simple and reliable detection of two different target miRNAs simultaneously at room temperature without any enzymatic reactions.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Molecular Medicine, University of Padua, via A. Gabelli 63, 35121 Padua, Italy.
i-Motifs (iMs) are quadruplex nucleic acid conformations that form in cytosine-rich regions. Because of their acidic pH dependence, iMs were thought to form only in vitro. The recent development of an iM-selective antibody, iMab, has allowed iM detection in cells, which revealed their presence at gene promoters and their cell cycle dependence.
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