ИСТИНА

Telomerase enzyme catalyses the elongation of 3'-ends of eukaryotic chromosomes. This activity is most important in actively proliferating cells where telomerase plays a key role in maintaining the length of telomeric DNA thus enabling cell division beyond the Hayflick limit. Inherited deficiency of telomerase activity due to mutations in telomerase components leads to telomeropathies, a wide spectrum of disorders associated with shortened telomeres. Their major manifestations are defects in stem-cell number and a deficiency in stem-cell regeneration, which can cause severe pathology up to multiorgan failure at early ages. From the other hand, abnormal activation of telomerase in cancer cells is a leading cause of their immortalisation. Recent biochemical, genetic and structural studies of telomerase components from different organisms contribute significantly to our understanding of telomerase function. Telomerase function is based on the dynamic interactions of its catalytic subunit (TERT) with nucleic acids—telomerase RNA, telomeric DNA and the DNA/RNA heteroduplex. Extremely low expression levels of telomerase, its multicomponent organisation and dynamic properties still represent major challenges for its structural characterisation. In our work we solved the structure of an essential N-terminal domain, or TEN, of TERT from thermotolerant yeast Hansenula polymorpha, using X-ray crystallography and NMR spectroscopy. The analysis of this structure in comparison with the known and homology modeled structures of TEN from other organisms demonstrates the structural conservation of the core motif in evolutionarily divergent organisms.