Volume 82, Nº 1 (2017)

This review considers the functions of extracellular actin–cell surface bound, associated with extracellular matrix, or freely circulating. The role of this protein in different pathological processes is analyzed: its toxic effects and involvement in autoimmune diseases as an autoantigen. The extracellular actin clearance system and its role in protection against the negative effects of actin are characterized. Levels of free-circulating actin, anti-actin immunoglobulins, and components of the actin clearance system as prognostic biomarkers for different diseases are reviewed. Experimental approaches to protection against excessive amounts of free-circulating F-actin are discussed.

Genome search of Bacillus subtilis revealed the presence of an open reading frame annotated as glutathione-dependent formaldehyde dehydrogenase/alcohol dehydrogenase. The open reading frame consists of 1137 nucleotides corresponding to a polypeptide of 378 amino acids. To examine whether the encoded protein is glutathione-dependent formaldehyde dehydrogenase or alcohol dehydrogenase, we cloned and characterized the gene product. Enzyme activity assays revealed that the enzyme exhibits a metal ion-dependent alcohol dehydrogenase activity but no glutathione-dependent formaldehyde dehydrogenase or aldehyde dismutase activity. Although the protein is of mesophilic origin, optimal temperature for the enzyme activity is 60°C. Thermostability analysis by circular dichroism spectroscopy revealed that the protein is stable up to 60°C. Presence or absence of metal ions in the reaction mixture did not affect the enzyme activity. However, metal ions were necessary at the time of protein production and folding. There was a marked difference in the enzyme activity and CD spectra of the proteins produced in the presence and absence of metal ions. The experimental results obtained in this study demonstrate that the enzyme is a bona-fide alcohol dehydrogenase and not a glutathionedependent formaldehyde dehydrogenase.

Manganese (Mn) is crucially important for vital activity of cells and has many biological functions. Nevertheless, high doses of Mn taken up by an organism over a long period may cause neurodegenerative diseases such as manganism and Parkinsonism. The molecular mechanisms of this Mn toxicity are still poorly studied. It is now believed that Mn-induced pathophysiological neural processes are multifaceted and affect several metabolic pathways. In particular, Mn ions might affect the processes of DNA replication and repair. To test this possibility, we obtained an SKOV-3 cell line resistant to the toxic action of Mn ions. We found that these cells are characterized by the activation of poly(ADP-ribose)polymerase, which leads to increased ability to repair DNA. Thus, the model used here supports the suggestion that at least one cause of Mn cytotoxicity might be disorders of the processes involved in DNA replication and repair.

Members of the genus Tobamovirus represent one of the best-characterized groups of plant positive, single stranded RNA viruses. Previous studies have shown that genomes of some tobamoviruses contain not only genes coding for coat protein, movement protein, and the cistron coding for different domains of RNA-polymerase, but also a gene, named ORF6, coding for a poorly conserved small protein. The amino acid sequences of ORF6 proteins encoded by different tobamoviruses are highly divergent. The potential role of ORF6 proteins in replication of tobamoviruses still needs to be elucidated. In this study, using biochemical and immunological methods, we have shown that ORF6 peptide is accumulated after infection in case of two isolates of Tobacco mosaic virus strain U1 (TMV-U1 common and TMV-U1 isolate A15). Unlike virus particles accumulating in the cytoplasm, the product of the ORF6 gene is found mainly in nuclei, which correlates with previously published data about transient expression of ORF6 isolated from TMV-U1. Moreover, we present new data showing the presence of ORF6 genes in genomes of several tobamoviruses. For example, in the genomes of other members of the tobamovirus subgroup 1, including Rehmannia mosaic virus, Paprika mild mottle virus, Tobacco mild green mosaic virus, Tomato mosaic virus, Tomato mottle mosaic virus, and Nigerian tobacco latent virus, sequence comparisons revealed the existence of a similar open reading frame like ORF6 of TMV.

Contrasting opinions on the role of extrinsic and intrinsic factors in cancer etiology (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78-81; Wu, S., et al. (2016) Nature, 529, 43-47) variously define priorities in the war on cancer. The correlation between the lifetime risk of several types of cancer and the total number of divisions of normal selfrenewing cells revealed by the authors has given them grounds to put forward the “bad luck” hypothesis. It assumes that ~70% of cancer variability is attributed to random errors arising during DNA replication in normal, noncancerous stem cells, i.e. to internal factors, which is impossible either to expect or to prevent. This assumption caused many critical responses that emphasize, on the contrary, the defining role of extrinsic factors in cancer etiology. The analysis of epidemio-logical and genetic data presented in this work testifies in favor of the “bad luck” hypothesis.

The opinion is presented according to which the “bad luck” hypothesis (Tomasetti, C., and Vogelstein, B. (2015) Science, 347, 78–81), which has recently received experimental confirmation, has the right to exist, and its criticisms are largely unfounded.