Telomerase RNA biosynthesis and processing.

Telomerase synthesizes repetitive G-rich sequences (telomeric repeats) at the ends of eukaryotic chromosomes. This mechanism maintains the integrity of the genome, as telomere shortening leads to degradation and fusion of chromosomes. The core components of telomerase are the telomerase catalytic subunit and telomerase RNA, which possesses a small template region serving for the synthesis of a telomeric repeat. Mutations in the telomerase RNA are associated with some cases of aplastic anemia and also cause dyskeratosis congenita, myelodysplasia, and pulmonary fibrosis. Telomerase is active in 85% of cancers, and telomerase activation is one of the first steps in cell transformation. The study of telomerase and pathways where this enzyme is involved will help to understand the mechanism of the mentioned diseases and to develop new approaches for their treatment. In this review we describe the modern conception of telomerase RNA biosynthesis, processing, and functioning in the three most studied systems - yeast, vertebrates, and ciliates.

Deamination of 5-methylcytosine residues in Mammalian cells.

DNA demethylation in mammalia occurs after fertilization and during embryogenesis and accompanies cell aging and cancer transformation. With the help of the primer extension reaction, MALDI MS and DNA cleavage by thymine DNA glycosylase deamination of 5-methylcytosine residues has been shown to take place when the model methylated DNA duplexes are treated with nuclear extracts from the cell lines CHO, HeLa, and Skov3. The hypothesis that deamination of 5-methylcytosine is the first stage of demethylation in mammalia has been postulated.