Nucleic Acids as Polymers

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (10 January 2023) | Viewed by 14180

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Guest Editor
Nanotechnology at the Institute of Biochemical Technology and Nanotechnology, Peoples' Friendship University of Russia, Moscow, Russia
Interests: biophysics; bionanotechnology; bioinformatics; thermodynamics; AFM; TEM; SEM
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Special Issue Information

Dear Colleagues,

The year 2023 will mark the 70th anniversary of the discovery of the DNA double helix in two consecutive papers that revealed how the physical and chemical properties of DNA define the processes that would later be recognized as the central dogma of molecular biology. The dogma shared the responsibilities in genome expression between DNA and RNA. Since then, scientists all over the world regularly discover novel and corrected well-known physical and chemical properties of both DNA and RNA. These contributions lead to either the formulation of new concepts in molecular biology or new inventions in biotechnology. Often, novel theories have left the given question unanswered but unearthed several more. This Special Issue is devoted to the reports on the physical and chemical properties of both DNA and RNA and explanations of how they are involved in their functioning.

Dr. Alexandre Vetcher
Guest Editor

Manuscript Submission Information

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Keywords

  • nucleic acids physical and chemical properties
  • nucleic acids bionanotechnology
  • nucleic acids structural properties
  • nucleic acids topology and spatial properties

Published Papers (7 papers)

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Research

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14 pages, 2541 KiB  
Article
Comprehensive Analysis of Chromatin Accessibility and Transcriptional Landscape Identified BRCA1 Repression as a Potential Pathological Factor for Keloid
by Kuixia Xie, Jingrun Yang, Qianqian Yao, Yang Xu, Yonglin Peng and Xinhua Liu
Polymers 2022, 14(16), 3391; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14163391 - 19 Aug 2022
Viewed by 1758
Abstract
Keloid is a poorly understood fibrotic skin disease that commonly occurs during wound-healing. As a polymer composed of nucleic acid and proteins, the structure of chromatin could be dynamically regulated in the nucleus. In this study, we explored the dynamics of chromatin accessibility [...] Read more.
Keloid is a poorly understood fibrotic skin disease that commonly occurs during wound-healing. As a polymer composed of nucleic acid and proteins, the structure of chromatin could be dynamically regulated in the nucleus. In this study, we explored the dynamics of chromatin accessibility and the transcriptome in dermal fibroblasts (DFs) in keloid formation. Compared to normal samples, chromatin accessibility and transcriptome were extensively altered in keloid DFs. In addition, changes in chromatin accessibility were closely associated with changes in gene expression in DFs. Breast cancer type 1 (BRCA1) was significantly downregulated in keloid DFs, and its knockdown promoted the proliferation and attenuated the migration ability of normal DF cells. Mechanistically, BRCA1 suppression significantly reduced the expression of neuronal pentraxin 2 (NPTX2), a cell viability-related gene. BRCA1 binding affinity at the NPTX2 enhancer and the chromatin accessibility in the same region were significantly lower in keloid DFs than in normal DFs, which might contribute to NPTX2 inhibition. In conclusion, this study identified BRCA1 inhibition in DFs as a novel pathological factor in keloids and preliminarily explored its potential mechanisms, which will help us understand the formation of keloids. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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17 pages, 5647 KiB  
Article
Design and Immunoinformatic Assessment of Candidate Multivariant mRNA Vaccine Construct against Immune Escape Variants of SARS-CoV-2
by Mushtaq Hussain, Anusha Amanullah, Ayesha Aslam, Fozia Raza, Shabana Arzoo, Iffat Waqar Qureshi, Humera Waheed, Nusrat Jabeen, Sanya Shabbir, Muneeba Ahsan Sayeed and Saeed Quraishy
Polymers 2022, 14(16), 3263; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14163263 - 10 Aug 2022
Cited by 3 | Viewed by 1924
Abstract
To effectively counter the evolving threat of SARS-CoV-2 variants, modifications and/or redesigning of mRNA vaccine construct are essentially required. Herein, the design and immunoinformatic assessment of a candidate novel mRNA vaccine construct, DOW-21, are discussed. Briefly, immunologically important domains, N-terminal domain (NTD) and [...] Read more.
To effectively counter the evolving threat of SARS-CoV-2 variants, modifications and/or redesigning of mRNA vaccine construct are essentially required. Herein, the design and immunoinformatic assessment of a candidate novel mRNA vaccine construct, DOW-21, are discussed. Briefly, immunologically important domains, N-terminal domain (NTD) and receptor binding domain (RBD), of the spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were assessed for sequence, structure, and epitope variations. Based on the assessment, a novel hypothetical NTD (h-NTD) and RBD (h-RBD) were designed to hold all overlapping immune escape variations. The construct sequence was then developed, where h-NTD and h-RBD were intervened by 10-mer gly-ala repeat and the terminals were flanked by regulatory sequences for better intracellular transportation and expression of the coding regions. The protein encoded by the construct holds structural attributes (RMSD NTD: 0.42 Å; RMSD RBD: 0.15 Å) found in the respective domains of SARS-CoV-2 immune escape variants. In addition, it provides coverage to the immunogenic sites of the respective domains found in SARS-CoV-2 variants. Later, the nucleotide sequence of the construct was optimized for GC ratio (56%) and microRNA binding sites to ensure smooth translation. Post-injection antibody titer was also predicted (~12000 AU) to be robust. In summary, the construct proposed in this study could potentially provide broad spectrum coverage in relation to SARS-CoV-2 immune escape variants. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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11 pages, 1676 KiB  
Article
Graphene Oxide and Fluorescent-Aptamer-Based Novel Aptasensors for Detection of Metastatic Colorectal Cancer Cells
by Hang Chen, Shurui Zhang, Yung-Chin Hsiao, Qun Wang, Jau-Song Yu and Wanming Li
Polymers 2022, 14(15), 3040; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14153040 - 27 Jul 2022
Cited by 4 | Viewed by 1437
Abstract
Early diagnosis of metastatic colorectal cancer (mCRC) is extremely critical to improve treatment and extend survival. W3 is an aptamer that can specifically bind to mCRC cells with high affinity. Graphene oxide (GO) is a two-dimensional graphitic carbon nanomaterial, which has widely used [...] Read more.
Early diagnosis of metastatic colorectal cancer (mCRC) is extremely critical to improve treatment and extend survival. W3 is an aptamer that can specifically bind to mCRC cells with high affinity. Graphene oxide (GO) is a two-dimensional graphitic carbon nanomaterial, which has widely used in constructing biosensors. In this study, we have developed a no-wash fluorescent aptasensor for one-step and sensitive detection of mCRC LoVo cells. It is based on fluorescence resonance energy transfer (FRET) between GO and the W3 aptamer labeled with 5-carboxyfluorescein (FAM). GO can quench the green fluorescence of the FAM-labeled W3 (FAM-W3). In the presence of the target cells, FAM-W3 preferentially binds the target cells and detaches from the surface of GO, leading to the fluorescence of FAM recovery. It was demonstrated that the fluorescence recovery increases linearly in a wide range of 0~107 cells/mL (R2 = 0.99). The GO-based FAM-labeled W3 aptasensor (denoted as FAM-W3-GO) not only specifically recognizes mCRC cell lines (LoVo and HCT116), but also sensitively differentiates the target cells from mixed cells, even in the presence of only 5% of the target cells. Furthermore, FAM-W3-GO was applied to detect LoVo cells in human whole blood, which showed good reproducibility with an RSD range of 1.49% to 1.80%. Therefore, FAM-W3-GO may have great potential for early diagnosis of mCRC. This strategy of GO-based fluorescent aptasensor provides a simple, one-step, and highly sensitive approach for the detection of mCRC cells. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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24 pages, 22160 KiB  
Article
Spontaneous DNA Synapsis by Forming Noncanonical Intermolecular Structures
by Viacheslav Severov, Vladimir Tsvetkov, Nikolay Barinov, Vladislav Babenko, Dmitry Klinov and Galina Pozmogova
Polymers 2022, 14(10), 2118; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14102118 - 23 May 2022
Cited by 2 | Viewed by 1717
Abstract
We report the spontaneous formation of DNA-DNA junctions in solution in the absence of proteins visualised using atomic force microscopy. The synapsis position fits with potential G-quadruplex (G4) sites. In contrast to the Holliday structure, these conjugates have an affinity for G4 antibodies. [...] Read more.
We report the spontaneous formation of DNA-DNA junctions in solution in the absence of proteins visualised using atomic force microscopy. The synapsis position fits with potential G-quadruplex (G4) sites. In contrast to the Holliday structure, these conjugates have an affinity for G4 antibodies. Molecular modelling was used to elucidate the possible G4/IM-synaptic complex structures. Our results indicate a new role of the intermolecular noncanonical structures in chromatin architecture and genomic rearrangement. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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10 pages, 4476 KiB  
Article
Novel Mutations in Putative Nicotinic Acid Phosphoribosyltransferases of Mycobacterium tuberculosis and Their Effect on Protein Thermodynamic Properties
by Yu-Juan Zhang, Muhammad Tahir Khan, Madeeha Shahzad Lodhi, Hadba Al-Amrah, Salma Saleh Alrdahe, Hanan Ali Alatawi and Doaa Bahaa Eldin Darwish
Polymers 2022, 14(8), 1623; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14081623 - 18 Apr 2022
Viewed by 1612
Abstract
pncB1 and pncB2 are two putative nicotinic acid phosphoribosyltransferases, playing a role in cofactor salvage and drug resistance in Mycobacterium tuberculosis. Mutations have been reported in first- and second-line drug targets, causing resistance. However, pncB1 and pncB2 mutational data are not available, [...] Read more.
pncB1 and pncB2 are two putative nicotinic acid phosphoribosyltransferases, playing a role in cofactor salvage and drug resistance in Mycobacterium tuberculosis. Mutations have been reported in first- and second-line drug targets, causing resistance. However, pncB1 and pncB2 mutational data are not available, and neither of their mutation effects have been investigated in protein structures. The current study has been designed to investigate mutations and also their effects on pncB1 and pncB2 structures. A total of 287 whole-genome sequenced data of drug-resistant Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa of Pakistan were retrieved (BioSample PRJEB32684, ERR2510337-ERR2510445, ERR2510546-ERR2510645) from NCBI. The genomic data were analyzed for pncB1 and pncB2 mutations using PhyResSE. All the samples harbored numerous synonymous and non-synonymous mutations in pncB1 and pncB2 except one. Mutations Pro447Ser, Arg286Arg, Gly127Ser, and delTCAGGCCG1499213>1499220 in pncB1 are novel and have not been reported in literature and TB databases. The most common non-synonymous mutations exhibited stabilizing effects on the pncB1 structure. Moreover, 36 out of 287 samples harbored two non-synonymous and 34 synonymous mutations in pncB2 among which the most common was Phe204Phe (TTT/TTC), present in 8 samples, which may have an important effect on the usage of specific codons that may increase the gene expression level or protein folding effect. Mutations Ser120Leu and Pro447Ser, which are present in the loop region, exhibited a gain in flexibility in the surrounding residues while Gly429Ala and Gly127Ser also demonstrated stabilizing effects on the protein structure. Inhibitors designed based on the most common pncB1 and pncB2 mutants may be a more useful strategy in high-burden countries. More studies are needed to elucidate the effect of synonymous mutations on organism phenotype. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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Review

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20 pages, 2847 KiB  
Review
Studies of the Mechanism of Nucleosome Dynamics: A Review on Multifactorial Regulation from Computational and Experimental Cases
by Danfeng Shi, Yuxin Huang and Chen Bai
Polymers 2023, 15(7), 1763; https://0-doi-org.brum.beds.ac.uk/10.3390/polym15071763 - 01 Apr 2023
Viewed by 2462
Abstract
The nucleosome, which organizes the long coil of genomic DNA in a highly condensed, polymeric way, is thought to be the basic unit of chromosomal structure. As the most important protein–DNA complex, its structural and dynamic features have been successively revealed in recent [...] Read more.
The nucleosome, which organizes the long coil of genomic DNA in a highly condensed, polymeric way, is thought to be the basic unit of chromosomal structure. As the most important protein–DNA complex, its structural and dynamic features have been successively revealed in recent years. However, its regulatory mechanism, which is modulated by multiple factors, still requires systemic discussion. This study summarizes the regulatory factors of the nucleosome’s dynamic features from the perspective of histone modification, DNA methylation, and the nucleosome-interacting factors (transcription factors and nucleosome-remodeling proteins and cations) and focuses on the research exploring the molecular mechanism through both computational and experimental approaches. The regulatory factors that affect the dynamic features of nucleosomes are also discussed in detail, such as unwrapping, wrapping, sliding, and stacking. Due to the complexity of the high-order topological structures of nucleosomes and the comprehensive effects of regulatory factors, the research on the functional modulation mechanism of nucleosomes has encountered great challenges. The integration of computational and experimental approaches, the construction of physical modes for nucleosomes, and the application of deep learning techniques will provide promising opportunities for further exploration. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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17 pages, 1537 KiB  
Review
Recent Development in Biomedical Applications of Oligonucleotides with Triplex-Forming Ability
by Incherah Bekkouche, Alexander Y. Shishonin and Alexandre A. Vetcher
Polymers 2023, 15(4), 858; https://0-doi-org.brum.beds.ac.uk/10.3390/polym15040858 - 09 Feb 2023
Cited by 4 | Viewed by 2145
Abstract
A DNA structure, known as triple-stranded DNA, is made up of three oligonucleotide chains that wind around one another to form a triple helix (TFO). Hoogsteen base pairing describes how triple-stranded DNA may be built at certain conditions by the attachment of the [...] Read more.
A DNA structure, known as triple-stranded DNA, is made up of three oligonucleotide chains that wind around one another to form a triple helix (TFO). Hoogsteen base pairing describes how triple-stranded DNA may be built at certain conditions by the attachment of the third strand to an RNA, PNA, or DNA, which might all be employed as oligonucleotide chains. In each of these situations, the oligonucleotides can be employed as an anchor, in conjunction with a specific bioactive chemical, or as a messenger that enables switching between transcription and replication through the triplex-forming zone. These data are also considered since various illnesses have been linked to the expansion of triplex-prone sequences. In light of metabolic acidosis and associated symptoms, some consideration is given to the impact of several low-molecular-weight compounds, including pH on triplex production in vivo. The review is focused on the development of biomedical oligonucleotides with triplexes. Full article
(This article belongs to the Special Issue Nucleic Acids as Polymers)
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