Volume 61, Nº 2 (2025)

NRF2 is a key component that is associated with protecting cells from damage. It is intersected by other signaling pathways that can have both direct and indirect effects on it. Proteins that can influence activity through acetylation and deacetylation, such as p300/CBP, HDACs and SIRT1, play an important role in these signaling pathways. But sometimes the research of different scientific groups contradict each other. On the one hand, there is evidence showing that acetylation increases the activity of NRF2, while deacetylation reduces the activity and level of transcripts of genes regulated by NRF2. On the other hand, some results show that activation of SIRT1 deacetylase increases the posttranslational activity of NRF2. At the same time, NRF2 itself affects the expression of SIRT1, forming a positive feedback loop. This review examines various aspects of the interaction between the activity of transcription factor NRF2 and acetylases/deacetylases, primarily SIRT1. In addition, variants of indirect interaction between NRF2 and SIRT1 through other signaling pathways associated with proteins such as PGC-1α and p62 are being considered.

We conducted the experiments of the short-term (1 hour) testing effect of the herbicide paraquat, one of the strongest inducer of oxidative stress, on cultured blood cells (late G1 stage of the first mitosis, 4 × 10^–8 mol/l) of 9 healthy donors. In 60-hour (short-term) and 120-hour (long-term) lymphocyte cultures exposed to paraquat in vitro, the average frequencies of aberrant cells were 4.05 ± 0.55 and 9.42 ± 1.23%, respectively, which significantly exceeds the corresponding control levels: 1.16 ± 0.30 and 1.70 ± 0.50% (p = 0.008 and p = 0.018, respectively). The observed genotoxic effects are primarily due to the induction of simple chromatid aberrations (single fragments), the levels of which were 3.32 ± 0.40 and 8.92 ± 1.40 per 100 cells as a result of short-term and long-term lymphocyte cultivation, respectively (in comparison with 1.03 ± 0.34 and 1.56 ± 0.38 per 100 cells in the corresponding control). The frequencies of paired chromosomal fragments in cell cultures of both types also significantly (or on the trend level) exceeded the control frequencies (p = 0.046 and p = 0.068 for 60- and 120-hour cultures, respectively). No differences were found between 60- and 120-hour unexposed cell cultures in the level of aberrant cells and chromosome aberrations of all types. In contrast, long-term lymphocyte cultures exposed to paraquat demonstrated significantly increased levels of aberrant metaphases and single chromatid fragments compared to short-term exposed cultures (p = 0.001). Long-term effects were shown to be characterized by higher individual values of Cohen's omega (w) – from 0.157 to 0.259, compared to those for 60-hour cultures – 0.057 to 0.153. The obtained data indicate the induction of genomic instability in distant descendants of human lymphocytes exposed to short-term paraquat at the beginning of cultivation, and its individual nature.

When DNA repair is completed, the processes associated with the restoration of the normal chromatin structure play an important role. Incorrect chromatin assembly can lead to genomic rearrangements, which, in turn, can cause the development of many diseases, including cancer. Previously, we showed that violations of the correct assembly of nucleosomes and their remodulation during the reparative assembly of chromatin lead to an increased level of mutagenesis. In this work, we have shown that the asf1Δ mutation has a constitutively hyperactivated Rad53 kinase, which causes disorganization of the chromatin structure and significantly changes the spectrum of spontaneous reparative mutations. Violation of the binding site of the Rad9 adaptive protein to DNA as a result of inactivation of the DOT1 gene eliminates hif1Δ-specific mutagenesis, which is a consequence of incorrect reparative assembly of nucleosomes. The absence of the Rad9 protein under normal growth conditions and when treated with low doses of UV rays leads to aberrant activation of the RNR complex. At the same time, a further increase in the dose of UV radiation practically does not affect the expression of RNR3. These results confirm that correct chromatin assembly is critical for the normal functioning of the genome.

Genetic diversity in populations from the western part of the Siberian stone pine, Pinus sibirica Du Tour, range was studied using the analysis of allozyme genotypes of adult trees. It was found that the Cis-Urals and Urals populations have similar patterns of genetic variability and are combined into two close groups that differ from the population from Western Siberia. The parameters of intrapopulation diversity of the studied samples in the western part of the range were lower than in the central part, according to previously obtained data. The clinal nature of variability at some allozyme loci, apparently, reflects both the dispersal of the species in a northwestern direction from the Ural refugium, and may be the result of adaptation of populations to the climatic conditions of the Cis-Urals and the Urals. The current dynamics of the range are due to climatic changes and anthropogenic influences, which cause fragmentation of the western border of the species' distribution and can lead to the extinction of individual island populations.

DNA sequencing of Soviet Merino sheep was performed to identify single nucleotide polymorphisms (ONP) in the GH and LEP genes associated with meat quality indicators. Based on the analysis, a missense mutation C.321C>T was found in the structure of the GH gene in exon 5, leading to the replacement of arginine with glycine; in the LEP gene in exon 3, a missense mutation C.387G>T was detected, which results in the replacement of the amino acid valine with leucine. The frequency of occurrence of alleles and genotypes in the detected single polymorphisms has been established. 321C>T of the GH gene and C.387G>T of the LEP gene. The relationship between the qualitative composition of muscle tissue in sheep and their genotypic variants for both studied genes has been revealed. The muscle tissue of the heterozygous genotype according to the mutant alleles C.321T of the GH gene and C.387>T of the LEP gene contained more protein by 3.3 and 2.4 abs.%, but less moisture by 3.3 and 2.4 abs.% than in sheep of the homozygous genotype according to the wild alleles C.321C of the GH gene and C.387G of the LEP gene. Studies of the longest back muscle of Soviet Merino sheep revealed a greater number of muscle fibers in carriers of mutant alleles C.321T of the GH gene and C.387>T of the LEP gene by 4.7 and 7.6%, but a smaller diameter of the muscle fiber by 8.9 and 5.0%, compared with muscle cells of sheep homozygous for wild alleles C.321C of the GH gene and C.387G of the LEP gene. The overall assessment of the "marbling" of muscle tissue in sheep of heterozygous genotypes for the mutant alleles C.321T of the GH gene and C.387>T of the LEP gene is 2.3 and 1.5 points higher than in homozygotes for the reference alleles C.321C of the GH gene and C.387G of the LEP gene. The results obtained allow us to consider the polymorphisms C.321C>T in the GH gene and C.387G>T in the LEP gene as genetic markers for evaluating and improving the quality of sheep meat.

For 18 Pyrenophora tritici-repentis strains the pathogenic micromycete causing tan spot of wheat, the race was determined and the ToxB/toxb genes were identified. The analyzed strains belonged predominantly to race 4, nonpathogenic for bread wheat. Alignment of the sequences of ToxB/toxb gene of one P. tritici-repentis strain from Kazakhstan and five strains from Tatarstan with the reference sequences of the ToxB1, toxb2, ToxB4, toxb12, and toxb14 genes allowed to accurately identify the genes analyzed in this study as toxb2. This is the first report of toxb2 gene in P. tritici-repentis populations from Russia and Kazakhstan. Also, the differences between the ToxB1 and toxb2 sequences were demonstrated: 27 nucleotide substitutions and one 3 bp deletion were found in the ORF region in ToxB1. In the 5’ UTR region of all obtained toxb2 sequences, as well as in reference ToxB1 sequences, the presence of four microsatellites (25 bp each) was detected between the TATA-box and the intron. In the toxb2 sequences of reference P. tritici-repentis strain SD20 and analyzed strains a 167 bp insertion was found in the 5’ UTR region before the intron. This insertion is not found in any known ToxB1 sequence and likely affects the functionality of toxb2 gene. Novel information on the structure of toxb2 gene has implications for understanding the evolution of ToxB/toxb genes of P. tritici-repentis.