[Three Important Discoveries in the Field of the Cytoskeleton's Proteins Functioning on the Drosophila melanogaster Model].

This review analyzes three studies carried out on Drosophila, which resulted in discoveries that would be impossible while using other subjects. Thanks to these discoveries, events accompanying the myoblast fusion process, the oocyte polarization, and the functioning of supracellular linear actomyosin cable-like structures coordinating the polarization of the cytoskeleton of the cell can be described in detail.

[Aryl-hydrocarbon receptor as a potential target for anticancer therapy]. / Aril-gidrokarbonovyi retseptor kak potentsial'naia mishen' dlia protivorakovoi terapii.

Aryl-hydrocarbon receptor (Aryl Hydrocarbon Receptor, AHR) is a ligand-dependent transcription factor, whose functions are related to xenobiotic detoxification, response to inflammation, and maintenance of tissue homeostasis. Recent investigations suggest that AHR also plays an important role in the processes of carcinogenesis. Increased expression of AHR is observed in several types of tumors and tumor cell lines. In addition, it turned out that the composition of pharmaceutical drugs used in oncotherapy includes some ligands AHR. These facts allow us to consider an aryl-hydrocarbon receptor as a potential target for anticancer therapy, especially for the treatment of severe cancers whose treatment options are very limited or do not exist at all. In this review the examples of AHR ligands' effect on tumor cell cultures and on model mice lines with AHR-dependent response are discussed.

[Overlapping genes and antisense transcription in eukaryotes].

Numerous studies showed that overlapping genes are fairly common elements of genome organization, not only in viruses and prokaryotes but also in eukaryotes. At the same time, the regulatory mechanisms of overlapping gene expression, as well as the functional relevance of antisense transcription, are still relatively unknown. This review describes the history of the discovery of regulatory antisense RNAs, the types of gene overlap, and the putative mechanisms of their functioning. In conclusion, the critical views of different authors on the problem of detecting overlapping genes and an evaluation of the level of antisense transcription are presented.

[Influence of hairpin RNA, specific to the gene lawc, on expression of overlapping genes of the lawc/Trf2 complex in D. melanogaster].

We used a genetic system of the gene complex leg-arista-wing complex/TBP related factor 2 (lawc/Trf2) as a suitable model for in vivo study of operational characteristics of divergent overlapping genes. We established lines of transgenic fruit flies carrying constructs capable of expressing hairpin RNA directed at post-transcriptional suppression of the mRNA gene lawc by way of RNA-interference. The attempt to artificially suppress lawc-transcripts caused a rise in the level of expression of the gene lawc by several times. It is shown that change in the concentration of lawc-transcripts can affect the concentration of Trf2 transcripts. Possible mechanisms of regulation of expression of the overlapping genes studied are discussed.

[Effect of mutations in lawc/Trf2 gene on development of chromocenter and chromosome disjunction in Drosophila melanogaster].

In Drosophila, one of the genes of the lawc/Trf2 (leg-arista-wing complex/TBP-related factor 2) complex encodes an alternative basic transcription factor homologous to the TRF2 protein in vertebrates and human and belongs to a conservative Tbp (TATA box-binding protein) gene family. In the present study, reasons for the high frequency of chromosome nondisjunction were studied among descendants of mutants from 18 lines with a decreased expression of the TRF2 protein. It was determined that the suppression of the TRF2 expression violates the development of a compact chromocenter and the correct approach of homologous chromosomes (in germinative and somatic cells). The possibility of the participation of TRF2 in the evolutionary genetically programmed process of sex-ratio violation, which is typical of a number of animal species, is discussed.

[Recovery of genomic regions affecting lawc/Trf2 expression during Drosophila melanogaster development].

Leg-arista-wing complex (lawc) mutations affect the expression of D. melanogaster proteins homologous to a human basic transcription factor, TBP (TATA-box binding protein) Related Factor 2 (TRF2), specifically involved in development. The paper for the first time reports the application of genetic screens for various genomic regions to recover genetic interactions between the lawc/Trf2 gene and other genes and genetic loci by using Deficiency Kit lines with small deletions in total providing maximal coverage of the genome. The deletion mapping allowed us to recover 26 genomic regions that, when deleted, are lethal or modify the mutant phenotype due to a decreased TRF2 expression level. These deletions could be useful in identifying both novel TRF2 targets and its positive and negative regulators. There is evidence that TRF2 can be a component of high molecular DNA Replication-related Element Factor (DREF)- and Nucleosome Remodeling Factor (NURF)-containing complexes. The present study for the first time reports new genetic interactions of lawc/Trf2 with genes that encode basic and specific transcription factors. In most cases, if mutated, those genes caused developmental defects or death of progeny. However, in the case of the e(y) 1 gene, coding for the Taf9 transcription factor, only the male reproductive system is impaired when the lawc/Trf2 phenotype is associated with a e(y)l gene mutation. Mutant lawc(p1)e(y)1(u1) males become infertile due to primary spermatocyte maturation arrest and impaired premeiotic chromosome condensation in germ cells.

[Gene expression modulation is an evolutionary resource of adaptive alterations in the morphogenesis of insect limbs].

Hypomorphic mutations have been investigated of the genes spineless (ss), Distal-less (Dll), leg-arista-wing complex/TBP-related factor 2(lawc/Trf2), CG5017, and hsp 70 in order to explore the effects of their expression level on the formation of distal structures of antenna and legs of Drosophila melanogaster. We demonstrated the effect of the CG5017, hsp 70, Dll, and lawc gene transcription level on phenotypic manifestation of the ss gene mutation and the involvement of these genes into morphogenesis regulation of Drosophila melanogaster limbs. The total decrease in the level of the CG5017, hsp 70, Dll, and laws gene expression level was shown to promote a loss of the segmented pattern of distal structures of legs and antennae and a reversion of Drosophila limb morphogenesis to the evolutionarily earlier progenitors of insects. A hypothesis is proposed considering limb morphogenesis of insects as an evolutionary ancient process of formation of amorphous-crystal chitin structures with catalytically modifying participation of gene expression products.