A V Anisimova, A A Evdokimova, M M Erokhin, D A Chetverina, N E Vorobyeva
{"title":"[Crol Promotes EcR Recruitment to Enhancers of Ecdysone- Dependent Genes in Drosophila melanogaster Salivary Glands].","authors":"A V Anisimova, A A Evdokimova, M M Erokhin, D A Chetverina, N E Vorobyeva","doi":"10.7868/S3034555326030094","DOIUrl":"https://doi.org/10.7868/S3034555326030094","url":null,"abstract":"<p><p>A set of genes activated by the hormone ecdysone has previously been identified in the salivary glands of wandering Drosophila larvae, along with a group of regulatory elements involved in transcriptional induction by ecdysone. New evidence was obtained to implicate the DNA-binding protein Crol in the transcriptional regulation of ecdysone-dependent genes in larval salivary glands. Crol was shown to bind to the promoters and enhancers of ecdysone-depending genes, demonstrating an increased binding in the salivary glands, where the genes are active, compared to brain tissue, where the genes are silent. Crol was found to prime the recruitment of the ecdysone receptor (EcR) at least on some ecdysone-dependent enhancers. Disruption of Crol binding at these sites in crol knockout larvae reduced the EcR binding level and decreased the transcriptional level of genes possessing the respective regulatory elements. Based on the findings, Crol was assumed to function as one of the many proteins that render regulatory regions susceptible to EcR binding, thereby enabling the specific effect of ecdysone on D. melanogaster tissues.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"501-516"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O E Shchigal, S P Korolev, A N Anisenko, M B Gottikh
{"title":"[WRN and Other RecQ Helicases in Life Cycles of Viruses].","authors":"O E Shchigal, S P Korolev, A N Anisenko, M B Gottikh","doi":"10.7868/S3034555326030053","DOIUrl":"https://doi.org/10.7868/S3034555326030053","url":null,"abstract":"<p><p>RecQ helicases are a conserved family of DNA-unwinding enzymes that play a key role in maintaining genomic stability by participating in DNA damage repair, recombination, replication, and telomere homeostasis. Five RecQ helicases are known in humans: BLM (the Bloom syndrome protein), WRN (Werner syndrome helicase), RECQL4, RECQL1, and RECQL5. All members of the RecQ family possess 3' → 5' helicase activity and are capable of unwinding DNA, including its complex secondary structures, in the 3'-to-5' direction by using the energy of ATP hydrolysis. WRN is unique among RecQ helicases in possessing additional 3' → 5' exonuclease activity, which expands its functionality in maintaining genomic stability. Mutations of the RecQ helicase genes lead to Werner, Bloom, and Rothmund-Thomson syndromes and are associated with a predisposition to cancer and premature aging. The enzymes consequently attract significant interest of the scientific community. Many viruses rely on host cell replication and repair mechanisms for their reproduction, and RecQ helicases may therefore influence the development of viral infections. The review discusses the role of RecQ helicases in replication of various viruses, including socially significant ones, such as the human immunodeficiency virus, herpes simplex virus, Epstein-Barr virus, hepatitis C virus, and others.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"440-456"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Omnipresent Lactate: Normalization of the Tumor Microenvironment as a Prerequisite for Any Anticancer Therapy].","authors":"K S Vishnyakova, X Pan, Y E Yegorov","doi":"10.7868/S3034555326030024","DOIUrl":"https://doi.org/10.7868/S3034555326030024","url":null,"abstract":"<p><p>The history of research on lactate is quite interesting. At first, it was considered an unnecessary product of glycolysis, which humans use only by converting it back into glucose (gluconeogenesis, Cori cycle). Then it turned out that it is a ready-made source of food for cells and, moreover, that some cells (neurons) may prefer it to glucose. Lactate receptors were discovered, and it became a regulator. Finally, in 2019 (after more than 200 years of study), the lactylation of histones and other proteins ( hundreds of targets) was discovered. Lactate became an epigenetic regulator. A single, very small molecule combines many functions. One of the main functions of interest to oncologists is that lactate, together with hypoxia, is a sign of supply dysfunction in the body and causes reactions aimed at normalization (angiogenesis, etc.). As a result, tumors, with the immune system silent, undergo \"normalization,\" with blood vessels growing in them to reduce hypoxia and the lactate concentration. In addition, in the tumor microenvironment, where the concentration of lactate is dozens of times higher than normal, lactate acts as an immunosuppressant. In recent years, antitumor therapy has been reoriented from targeting tumor cells themselves to targeting immune cells (using \"checkpoints\"). Lactate has become one of the targets of such therapy. Various aspects of the molecular biology of lactate are covered in this review. Particular attention is paid to the role of lactate in antitumor therapy.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"389-413"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
O A Zemlianaia, A V Efremova, V V Strelnikov, D V Zaletaev
{"title":"[DNA Methylation as a Biomarker for Chromatinopathies: Present and Future].","authors":"O A Zemlianaia, A V Efremova, V V Strelnikov, D V Zaletaev","doi":"10.7868/S3034555326030032","DOIUrl":"https://doi.org/10.7868/S3034555326030032","url":null,"abstract":"<p><p>With the widespread adoption of wide- and whole-genome massively parallel sequencing methods, the capabilities of molecular genetic diagnostics of hereditary diseases have expanded significantly. However, the challenge of increasing the detection rate of certain nosologies remains relevant. In recent decades, the use of DNA methylation as a biomarker for pathological conditions, including damage to the epigenetic machinery, has been extensively explored and discussed. Thus, DNA methylation can act as an indicator of damage to the epigenetic machinery. The analysis of the genome methylation pattern can be used to optimize the diagnosis of chromatinopathies, hereditary diseases caused by the emergence of a pathogenic variant in a nucleotide sequence in one of the genes controlling the epigenetic landscape. Highly specific changes in the DNA methylation pattern, or episignature, were identified for over 70 syndromes of this group improving the effectiveness of their differential diagnosis. This review examines the molecular basis for the emergence of the episignatures, the principles of their identification, distinctive features, possibilities and limitations of application, and prospects for the development of methods for analyzing changes in DNA methylation patterns as one of the areas of chromatinopathy diagnostics.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"414-429"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D R Kharrasov, G Yu Fisunov, D S Matyushkina, E A Tsoy, E A Semenova, R R Kutukov, I S Rog, D A Sandanova, M M Borodina, V M Govorun
{"title":"[Cloning of Mycoplasma gallisepticum Genome in Saccharomyces cerevisiae Cells].","authors":"D R Kharrasov, G Yu Fisunov, D S Matyushkina, E A Tsoy, E A Semenova, R R Kutukov, I S Rog, D A Sandanova, M M Borodina, V M Govorun","doi":"10.7868/S3034555326030072","DOIUrl":"https://doi.org/10.7868/S3034555326030072","url":null,"abstract":"<p><p>To date, the genomes of several mycoplasmas have been cloned in Saccharomyces cerevisiae cells, including Mycoplasma genitalium, M. pneumoniae, and M. mycoides. In this work, the 1-Mb genome of Mycoplasma gallisepticum S6 was cloned in S. cerevisiae. A transposon vector was constructed to deliver a synthetic S. cerevisiae replicon and a selective marker into M. gallisepticum genome. Transplantation of the M. gallisepticum genome with the integrated yeast replicon to yeast cells was performed using two approaches, polyethylene glycol (PEG)-induced transformation of yeast spheroplasts with intact genomic DNA isolated from M. gallisepticum cells and prepared in aragose plugs and PEG-induced fusion of M. gallisepticum cells with yeast spheroplasts. Both of the approaches yielded S. cerevisiae strains with the cloned M. gallisepticum genome, as was verified by nanopore sequencing.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"474-485"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N O Kudryashova, V A Dolgusheva, I V Dobrokhotov, Sh Sh Nasayev, A A Moskalev
{"title":"[Modern Methods of Molecular Modeling of Aptamers].","authors":"N O Kudryashova, V A Dolgusheva, I V Dobrokhotov, Sh Sh Nasayev, A A Moskalev","doi":"10.7868/S3034555326030019","DOIUrl":"https://doi.org/10.7868/S3034555326030019","url":null,"abstract":"<p><p>Aptamers are short single-stranded nucleic acid molecules with a unique ability to bind with high specificity andaffinity to a wide range of biomolecules, including proteins, viruses, and small molecules, due to the formation of tertiary structures, making them a powerful alternative to antibodies in biosensing, diagnostics, and therapy. Their advantages, such as high stability, the possibility of targeted chemical modification, and reproducible solid-phase synthesis without the use of cell-based systems or bioreactors, have driven the active development of methods for their design and optimization. This review systematizes the key stages in the evolution of aptamer development technologies, starting with the classic SELEX technology, and considers its modifications, including CE-SELEX, M-SELEX, Cell-SELEX, HT-SELEX, and others, aimed at improving the efficiency, specificity, and automation of the process. Special attention is paid to the integration of computational methods such as secondary and tertiary structure prediction (RNAfold, MXfold2, RNAComposer), molecular docking (AutoDock Vina, HADDOCK, ZDOCK), molecular dynamics (GROMACS, AMBER, NAMD), and SELEX data analysis (AptaSUITE, FASTAptamer). The implementation of machine learning and deep learning algorithms (AptaDiff, RaptGen, Apta-MCTS, Xelari) is also described, opening up new opportunities for the rational design of de novo aptamers, optimization of their affinity, and minimization of experimental costs. The review discusses the limitations of the current methods, such as limited amount of structural data, the complexity of predicting noncanonical pairs and pseudoknots, and the insufficient generalizability of ML models to new sequence families. This review highlights the transformative potential of aptamers in biomedicine but emphasizes the need for rigorous experimental validation of computational predictions to overcome current limitations.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"367-388"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A O Sosnovtseva, E S Starodubova, D S Karpov, V L Karpov
{"title":"[Yeast as a Biochemical Model for Diseases Associated with Impaired Intracellular Proteolytic Systems].","authors":"A O Sosnovtseva, E S Starodubova, D S Karpov, V L Karpov","doi":"10.7868/S3034555326030045","DOIUrl":"https://doi.org/10.7868/S3034555326030045","url":null,"abstract":"<p><p>The degradation of intracellular proteins is a fundamental biological process necessary for maintaining cellular homeostasis, controlling the cell cycle, regulating signal transduction, and preventing the accumulation of toxic protein aggregates. Disorders of the proteolytic systems are implicated in the pathogenesis of numerous human diseases, including neurodegenerative diseases, lysosomal storage disorders, metabolic disorders, and certain types of cancer. The development of rudimentary and cost-effective models of these diseases for the purpose of evaluating novel pharmaceutical agents and elucidating the molecular mechanisms underlying disease pathogenesis constitutes a pivotal medical and biological undertaking. The proteolytic apparatus of the yeast species Saccharomyces cerevisiae has become a biochemical model organism of significant importance. This is due to its well-studied nature, low cost, ease of genetic manipulation, and evolutionary conservatism. The mechanisms of proteolytic system dysfunction can be studied in this organism. Furthermore, therapeutic approaches aimed at correcting these dysfunctional mechanisms can be sought.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"430-439"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N V Petrova, N G Syrchina, A A Mikhailova, P V Mikshina, N E Mokshina
{"title":"[Optimization of Plant Recombinant Lectin Production Using a Transient Expression System in Nicotiana benthamiana].","authors":"N V Petrova, N G Syrchina, A A Mikhailova, P V Mikshina, N E Mokshina","doi":"10.7868/S3034555326030088","DOIUrl":"https://doi.org/10.7868/S3034555326030088","url":null,"abstract":"<p><p>Lectins are proteins capable of specifically recognizing and reversibly binding carbohydrates, but they lack enzymatic activity toward their bound molecules. Through this carbohydrate recognition, lectins play key roles in regulating physiological and defense processes in organisms. To obtain functionally active plant recombinant lectins, it is necessary to use expression systems that can provide correct post-translational modifications, including glycosylation, which is impossible when expressing proteins in bacterial cells. Transient expression of plant proteins in leaves enables the formation of a proper modification profile and ensures high reproducibility. This work presents an optimized protocol for obtaining recombinant flax lectins using the method of transient expression in Nicotiana benthamiana leaves. The protocol encompasses all stages, from primer design and molecular cloning to the production of purified protein and the subsequent assessment of N-glycosylation.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"486-500"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
V V Tiguntsev, I A Mednova, A N Kornetov, D Z Paderina, E G Kornetova, S A Ivanova
{"title":"[The Search for Associations of Polymorphic Variants of the COMT and MAOA Genes with Suicide Attempts in Patients with Schizophrenia: A Pilot Study].","authors":"V V Tiguntsev, I A Mednova, A N Kornetov, D Z Paderina, E G Kornetova, S A Ivanova","doi":"10.7868/S3034555326030061","DOIUrl":"https://doi.org/10.7868/S3034555326030061","url":null,"abstract":"<p><p>The main causes of early mortality in patients with schizophrenia are comorbid somatic diseases (primarily cardiovascular diseases, diabetes, and obesity) and suicide, which reduces life expectancy on average by ten years compared to the general population. The COMT gene encodes catechol-O-methyltransfer- ase. This enzyme is responsible for O-methylation, one of the main pathways for catecholamine inactivation. The MAOA gene encodes monoaminoxidаse type A, an enzyme that carries out oxidative deamination of dopamine, norepinephrine, and serotonin. We hypothesized that polymorphic variants of the COMT and MAOA genes are associated with suicidal behavior in patients with schizophrenia. Accordingly, the aim of our study was to investigate the associations between the presence or absence of a history of suicidal behavior in patients with schizophrenia and polymorphic variants of the COMT and MAOA genes. A total of 150 patients of Slavic ethnicity with schizophrenia were examined. The presence or absence of a history of suicidal tendencies was determined based on medical records and a clinical interview. The control group consisted of 134 apparently healthy military personnel. Seven polymorphic variants in the COMT gene and two polymorphic variants in the MAOA gene were selected for pilot genotyping. Polymorphic variants of the COMT and MAOA genes were initially determined using PCR. An association was found between the COMT rs4680 and rs4633 polymorphic variants and a history of suicide attempts in patients with schizophrenia. The results of our study demonstrate the possible contribution of the catechol-O-methyltransferase gene to the mechanisms of suicidal behavior in patients with schizophrenia.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"457-473"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I V Margatskiy, A M Eliseikin, V E Artemov, I O Ponkratenko, A E Studennikov, A N Glushkov
{"title":"[Effect of ESR1 Somatic Mutations on SERM/SERD Binding: Insights from Molecular Docking and Molecular Dynamics Simulations].","authors":"I V Margatskiy, A M Eliseikin, V E Artemov, I O Ponkratenko, A E Studennikov, A N Glushkov","doi":"10.7868/S3034555326030107","DOIUrl":"https://doi.org/10.7868/S3034555326030107","url":null,"abstract":"<p><p>Acquired resistance to endocrine therapy poses a major limitation in the treatment of estrogen receptor (ER)-positive breast cancer (BC). Somatic mutations of the ESR1 gene, which encodes ERα, are one of the key resistance mechanisms. However, the effect of mutations and especially double mutations on the binding of novel drugs remains insufficiently understood. To evaluate the effect of the mutations at the molecular level, a comprehensive computational approach was employed, including molecular docking, binding free energy calculations (MM-GBSA), and molecular dynamics simulations. A comparative analysis revealed opposite effects of ESR1 mutations on affinities of various selective ER degraders (SERDs). Vepdegestrant and fulvestrant were found to bind far less efficiently with ERα mutants and especially double mutants (e.g., Y537C/D538G) than with the native ERα. In contrast, the SERD ZB716 demonstrated the same or even better binding with most mutants. A potential structural cause of its resilience to mutations was identified via a comprehensive analysis, which included the evaluation of individual amino acid residue mobility through root-mean-square fluctuation (RMSF) calculations and an assessment of intermolecular hydrogen bond stability. ZB716 was shown to maintain a stable hydrogen bond with Glu353, and the bond was preserved in the ERα mutants. A lower stability of this key interaction was observed with fulvestrant. The findings elucidate the molecular mechanism of ESR1 mutation-driven resistance and support the promise of ZB716 as a compound capable of overcoming resistance conferred by a subset of the most common somatic ESR1 mutations in BC patients. The results justify the targeted design of new SERDs aimed at interacting with ERα mutants and outline an avenue of further research in the field of personalized therapy for ER+ BC.</p>","PeriodicalId":39818,"journal":{"name":"Molekulyarnaya Biologiya","volume":"60 3","pages":"517-530"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148762578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}