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44 results on '"Dolinnaya, Nina G."'

4. Crosstalk between G-Quadruplexes and Dnmt3a-Mediated Methylation of the c-MYC Oncogene Promoter.

Author

Sergeev, Alexander V., Loiko, Andrei G., Genatullina, Adelya I., Petrov, Alexander S., Kubareva, Elena A., Dolinnaya, Nina G., and Gromova, Elizaveta S.

Subjects
QUADRUPLEX nucleic acids, METHYLATION, ONCOGENES, DNA structure, GENETIC regulation
Abstract

The methylation of cytosines at CpG sites in DNA, carried out de novo by DNA methyltransferase Dnmt3a, is a basic epigenetic modification involved in gene regulation and genome stability. Aberrant CpG methylation in gene promoters leads to oncogenesis. In oncogene promoters, CpG sites often colocalize with guanine-rich sequences capable of folding into G-quadruplexes (G4s). Our in vitro study aimed to investigate how parallel G4s formed by a sequence derived from the c-MYC oncogene promoter region affect the activity of the Dnmt3a catalytic domain (Dnmt3a-CD). For this purpose, we designed synthetic oligonucleotide constructs: a c-MYC G4-forming oligonucleotide and linear double-stranded DNA containing an embedded stable extrahelical c-MYC G4. The topology and thermal stability of G4 structures in these DNA models were analyzed using physicochemical techniques. We showed that Dnmt3a-CD specifically binds to an oligonucleotide containing c-MYC G4, resulting in inhibition of its methylation activity. c-MYC G4 formation in a double-stranded context significantly reduces Dnmt3a-CD-induced methylation of a CpG site located in close proximity to the quadruplex structure; this effect depends on the distance between the non-canonical structure and the specific CpG site. One would expect DNA hypomethylation near the G4 structure, while regions distant from this non-canonical form would maintain a regular pattern of high methylation levels. We hypothesize that the G4 structure sequesters the Dnmt3a-CD and impedes its proper binding to B-DNA, resulting in hypomethylation and activation of c-MYC transcription. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Bioinformatics Analysis of Global Diversity in Meningococcal Vaccine Antigens over the Past 10 Years: Vaccine Efficacy Prognosis.

Author

Savitskaya, Viktoriia Yu., Dolinnaya, Nina G., Strekalovskikh, Vadim V., Peskovatskova, Elizaveta S., Snyga, Viktoriia G., Trefilov, Vadim S., Monakhova, Mayya V., and Kubareva, Elena A.

Subjects
NEISSERIA, MENINGOCOCCAL infections, MENINGOCOCCAL vaccines, VACCINE effectiveness, AMINO acid sequence, ANTIGENS, NEISSERIA meningitidis
Abstract

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Effects of G-Quadruplex-Binding Plant Secondary Metabolites on c-MYC Expression

Author

Zenkov, Roman G., primary, Kirsanov, Kirill I., additional, Ogloblina, Anna M., additional, Vlasova, Olga A., additional, Naberezhnov, Denis S., additional, Karpechenko, Natalia Y., additional, Fetisov, Timur I., additional, Lesovaya, Ekaterina A., additional, Belitsky, Gennady A., additional, Dolinnaya, Nina G., additional, and Yakubovskaya, Marianna G., additional

Published
2022
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16. Responses of DNA Mismatch Repair Proteins to a Stable G-Quadruplex Embedded into a DNA Duplex Structure

Author

Pavlova, Anzhela V., primary, Monakhova, Mayya V., additional, Ogloblina, Anna M., additional, Andreeva, Natalia A., additional, Laptev, Gennady Yu., additional, Polshakov, Vladimir I., additional, Gromova, Elizaveta S., additional, Zvereva, Maria I., additional, Yakubovskaya, Marianna G., additional, Oretskaya, Tatiana S., additional, Kubareva, Elena A., additional, and Dolinnaya, Nina G., additional

Published
2020
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21. Molecular and thermodynamic properties of d(A+-G)10, a single-stranded nucleic acid helix without paired or stacked bases

Author

Dolinnaya, Nina G., Braswell, Emory H., Fossella, John A., Klump, Horst, and Fresco, Jacques R.

Subjects
Nucleotide sequence -- Evaluation, Thermodynamic potentials -- Measurement, Molecular biology -- Research, Biological sciences, Chemistry
Abstract

Deoxyoligonucleotide d(A+-G)10 has a secondary conformation which is basically helical and intramolecular. Positively charged adenine residues and distal negatively charged phosphates reveal ionic bonds between them which are used to stabilize the secondary conformation. A solitary strand molecular weight is obtained for the d(A+-G)10 by sedimentation equilibrium. The disturbance of the helix does not reveal modifications in the molecular weight. Cooperative uptake of nine protons are seen with the production of the d(A+-G)10 helix.

Published
1993

23. Single-stranded nucleic acid helical secondary structure stabilized by ionic bonds: d(A+ -G)(sub 10)

Author

Dolinnaya, Nina G. and Fresco, Jacques R.

Subjects
Nucleic acids -- Analysis, DNA -- Analysis, Science and technology
Abstract

A new type of helical secondary structure for single-stranded nucleic acids is described. The structure was deduced from UV and CD spectroscopic analyses of a homopurine oligomer d(A-G)10 below pH 6 in 0.01 M Na+. The structure, designated d(A+ -G)10, occurs in neutral pH as a multistranded helical structure stabilized by base stacking and hydrogen bonding between pairs or tetrads on bases. Upon protonation, the CD of the structure intensifies, with only minor hypochromicity. It is proposed that this structure may contribute in the stabilization of intramolecular DNA triplexes.

Published
1992

41. Design and Synthesis of 2'-Functionalised Oligonucleotides. Their Application for Covalent Trapping the Protein - DNA Complexes

Author

Dolinnaya, Nina G., Zubin, Eugeny M., Kubareva, Elena A., Zatsepin, Timofey S., and Oretskaya, Tatiana S.

Abstract

This review outlines the design and synthesis of oligonucleotides bearing 2'-modified residues at predetermined positions within the strand. The relative merits of incorporation of reactive carboxyl, carbonyl, iodoacetamide and disulfide-containing groups into oligonucleotides were considered along with solid-phase synthesis of DNA 2'- conjugates. The specific cross-linking of 2'-substituted oligonucleotides to nucleic acid-binding proteins (transcription factor NF-κB, restriction-modification enzymes) was shown to be helpful in scanning the protein-DNA interface and studying the conformational dynamics of biopolymer ensembles. The future perspectives of chemically reactive DNA constructs as specific protein decoys are discussed.

Published
2009

43. Parallel-Stranded Linear Homoduplexes of d(A+-G)/n > 10 and d(A-G)n > 10 Manifesting the Contrasting Ionic Strength Sensitivities of Poly(A+{middle dot}A+) and DNA

Author

Dolinnaya, Nina G., Ulku, Aylin, and Fresco, Jacques R.

Abstract

In contrast to shorter homologs which only form a single-stranded nucleic acid α-helix in acid solution at [Na+] ≤ 0.02 M Na+, d(A-G)20,30 form in addition a parallel-stranded duplex with (A+·A+) and (G·G) base pairs and interstrand dA+…PO2− ionic and dA+NH2…O=P H-bonds. Under conditions where duplex prevails over α-helix, the contribution of the base-backbone interactions to stability varies directly with [H+] and inversely with [Na+], just as in poly(A+·A+). These duplexes are characterized by intense circular dichroism and a large cooperative thermally-induced hyperchromic transition that is dependent on oligomer concentration. Dimethylsulfate reactivity of the dG residues indicates G·G and therefore dA+·dA+ rather than dA+·G base pairs. At much higher ionic strength (Na+ ≥ 0.2 M) the protonated base-backbone interactions are so weakened that duplex stability becomes increasingly dependent upon H-bonded base pairing and stacking and almost independent of pH. Between pH 6 and 8 this duplex structure is devoid of protonated dA residues and shows positive dependence of Tm on ionic strength similar to that of DNA.

Published
1997
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44. Toward G-Quadruplex-Based Anticancer Agents: Biophysical and Biological Studies of Novel AS1411 Derivatives

Author

Emanuele Ugo Garzarella, Sonia Di Gaetano, Nunzia Iaccarino, Domenica Capasso, Anna M. Ogloblina, Marianna G. Yakubovskaya, Bruno Pagano, Nina G. Dolinnaya, Jussara Amato, Antonio Randazzo, Ogloblina, Anna M, Iaccarino, Nunzia, Capasso, Domenica, Di Gaetano, Sonia, Garzarella, Emanuele U, Dolinnaya, Nina G, Yakubovskaya, Marianna G, Pagano, Bruno, Amato, Jussara, and Randazzo, Antonio

Subjects
0301 basic medicine, Circular dichroism, Magnetic Resonance Spectroscopy, Apoptosis, 01 natural sciences, lcsh:Chemistry, Drug Stability, Fluorescence Resonance Energy Transfer, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, Deoxyribonucleases, biology, G-quadruplex, Circular Dichroism, Nucleic Acid Heteroduplexes, RNA-Binding Proteins, General Medicine, Aptamers, Nucleotide, Computer Science Applications, Biochemistry, DNA Topoisomerases, Type I, Oligodeoxyribonucleotides, MCF-7 Cells, Female, in vitro biological assays, guanine-rich oligonucleotides, guanine-rich oligonucleotide, biophysical characterization, antiproliferative activity, Cancer therapy, Antineoplastic Agents, in vitro biological assay, 010402 general chemistry, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, nucleolin, Humans, Physical and Theoretical Chemistry, Molecular Biology, Biological studies, Oligonucleotide, Topoisomerase, Organic Chemistry, Surface Plasmon Resonance, Phosphoproteins, 0104 chemical sciences, 030104 developmental biology, Enzyme, chemistry, lcsh:Biology (General), lcsh:QD1-999, biology.protein, Drug Screening Assays, Antitumor, Topoisomerase I Inhibitors, Nucleolin, Thymine
Abstract

Certain G-quadruplex forming guanine-rich oligonucleotides (GROs), including AS1411, are endowed with cancer-selective antiproliferative activity. They are known to bind to nucleolin protein, resulting in the inhibition of nucleolin-mediated phenomena. However, multiple nucleolin-independent biological effects of GROs have also been reported, allowing them to be considered promising candidates for multi-targeted cancer therapy. Herein, with the aim of optimizing AS1411 structural features to find GROs with improved anticancer properties, we have studied a small library of AS1411 derivatives differing in the sequence length and base composition. The AS1411 derivatives were characterized by using circular dichroism and nuclear magnetic resonance spectroscopies and then investigated for their enzymatic resistance in serum and nuclear extract, as well as for their ability to bind nucleolin, inhibit topoisomerase I, and affect the viability of MCF-7 human breast adenocarcinoma cells. All derivatives showed higher thermal stability and inhibitory effect against topoisomerase I than AS1411. In addition, most of them showed an improved antiproliferative activity on MCF-7 cells compared to AS1411 despite a weaker binding to nucleolin. Our results support the hypothesis that the antiproliferative properties of GROs are due to multi-targeted effects.

Published
2020

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