M. E. Zvereva

Telomerase: Structure and properties of the enzyme, and peculiarities of yeast telomerase

Telomerase is a ribonucleoprotein that extends telomeric ends of chromosomes to counterbalance their natural shortening due to incomplete DNA replication in eukaryotic cells. The core enzyme consists of the catalytic reverse transcriptase subunit TERT (Telomerase Reverse Transcriptase) and the RNA subunit TER (Telomerase RNA), a short specific region of which serves as a template for synthesis of telomeric repeats. Despite the intensive research of telomerase in different organisms, the mechanism of its action remains unclear. This review focuses on telomerase of yeast Saccharomyces cerevisiae. Unlike ciliate and human telomerases, the yeast enzyme adds only one telomeric repeat to the DNA oligonucleotide (primer), imitating the single-stranded telomeric end of a chromosome, and remains stably bound to it after elongation in vitro. This review summarizes the results of numerous studies on the structure and functions of the core enzyme components, their interactions with each other and a primer, and telomerase activity on different substrates in vitro. The peculiarities of telomerase functioning in a cell and accessory proteins of the telomerase complex are also discussed.

Recombinogenic Telomeres in Diploid Sorex granarius (Soricidae, Eulipotyphla) Fibroblast Cells

ABSTRACT The telomere structure in the Iberian shrew Sorex granarius is characterized by unique, striking features, with short arms of acrocentric chromosomes carrying extremely long telomeres (up to 300 kb) with interspersed ribosomal DNA (rDNA) repeat blocks. In this work, we investigated the telomere physiology of S. granarius fibroblast cells and found that telomere repeats are transcribed on both strands and that there is no telomere-dependent senescence mechanism. Although telomerase activity is detectable throughout cell culture and appears to act on both short and long telomeres, we also discovered that signatures of a recombinogenic activity are omnipresent, including telomere-sister chromatid exchanges, formation of alternative lengthening of telomeres (ALT)-associated PML-like bodies, production of telomere circles, and a high frequency of telomeres carrying marks of a DNA damage response. Our results suggest that recombination participates in the maintenance of the very long telomeres in normal S. granarius fibroblasts. We discuss the possible interplay between the interspersed telomere and rDNA repeats in the stabilization of the very long telomeres in this organism.

Expression of genes involved in DNA repair and telomere maintenance in the yeast Hansenula polymorpha DL1 under heat stress

185 Methylotrophic yeasts are widely used to study methanol metabolism, biogenesis and functions of peroxisomes, and as a “biofactory” to produce recom binant proteins. A characteristic feature of the Hansenula polymorpha DL1 strain ATCC 26012 is thermotolerance: these yeasts can grow at tempera tures up to 50°C [1]. This ability determines the higher thermal stability of proteins and nucleoprotein com plexes of these yeasts, which makes them an interest ing model object for studying the molecular processes such as DNA repair and telomere formation [2]. Pre viously, we determined the complete nucleotide sequence of the mitochondrial and nuclear genome of H. polymorpha DL1 and analyzed transcription when this strain was growth on glucose medium or methanol [3, 4].

Telomerase as a potential marker for early diagnosing cervical carcinoma.

158 A tumor cell differs from the normal one in both genetic and epigenetic changes. Among the latter, DNA methylation and telomerase activation are of special importance. Telomerase activation in tumors is a ubiquitous phenomenon characteristic of most tumor cells [1]. This activity is not characteristic of normal cells, but it is detected in immortal cells grown in vitro [2], as well as in stem and germinal cells [3].

Structure and Function of tmRNA (10Sa RNA)

Modern data on the structure and function of transport/messenger (tm) RNA are reviewed. This stable RNA is involved in releasing ribosomes that are unable to complete protein synthesis on mRNA lacking the stop codon. The resulting abnormal proteins are rapidly degraded by specific proteases, which recognize a signal peptide encoded by the template region of tmRNA. The discovery of trans-translation has caused a particular interest in structural and functional studies of tmRNA.

Identification of additional telomerase component of the yeast H. polymorpha is a step towards understanding the complex at the atomic level

59 Telomerase is a ribonucleoprotein complex whose function is to synthesize telomeres—repeated sequences at the ends of linear chromosomes. The absence of telomerase activity in the cell causes grad ual shortening of telomeres, with the onset of senes cence after reaching the critical length. In addition to the catalytic subunit and telomerase RNA, additional components are required for the functioning of this enzyme in vivo in the yeast S. cerevisiae cells, namely, Est1 and Est3. To date, structural data for these com ponents are absent due to the instability of the pro teins.

DNA as a nanomateria

This review discusses information about the use of DNA as a basis for preparing materials with new properties. The unique molecular recognition property of nucleic acids that underlies the synthesis of targeted controllable structures, where DNA functions as an engineering material rather than a genetic-information carrier, is considered. Causes of significant advances in this field are discussed. The new functional potential of novel materials is examined.

trans-Translation: The Main Participants and the Role in Cell Life

Abstracttrans-Translation is the unique process of synthesizing a single polypeptide chain from both mRNA and the coding region of transport–messenger RNA (tmRNA). It is necessary for cell vital activity in the changing environment. New data on the main participants of trans-translation, conditions under which it occurs, and its role in the cell are reviewed. The possible role of tmRNA in translation quality control is discussed.

Telomerase activity in peripheral blood mononuclear cells as a universal scale for quantitative measurement of telomerase activation on the example of liver diseases

Telomerase is a ribonucleoprotein complex con sisting of telomerase RNA, telomerase reverse tran scriptase (TERT), and a number of associated pro teins. TERT synthesizes repeated DNA sequences at the ends of chromosome using a template region of telomerase RNA [2]. The number of such repeats (telomere length) corresponds to the possible number of cell divisions and determines the proliferative potential of the cell [2].

High expression levels and nuclear localization of novel Danio rerio ncRNA transcribed from a genomic region containing repetitive elements

Noncoding and repetitive sequences make up a large part of the genome of high eukaryotes, but the elucidation of their roles and mechanisms of action are poorly understood. In this work, we found that interstitial telomeric repeats in the genome of Danio rerio colocalize with repetitive elements, including hAT and EnSpm, which are widely represented in vertebrate genomes. The investigation of a genomic region containing two pairs of these repeats located in close proximity showed that the area is transcribed. RNA-dependent structures containing this sequence were identified in D. rerio fibroblast nuclei, which indicates the functional importance of genomic repetitive elements or their transcripts.