ИСТИНА

Telomerase is a ribonucleoprotein complex responsible for the elongation of telomeric repeats and maintenance of genome integrity. Its hyperactivation provides a characteristic signature for the majority of cancers, while its down-regulation is associated with ageing and several early cell death related pathologies. In this light modulation of telomerase activity is an attractive route of finding new therapeutics. The lack of structural information hampers development of telomerase modulators. Here we present the NMR study of structures and functions of two proteins from yeast Hansenula Polymorpha telomerase complex: TEN-domain of telomerase catalytic subunit [1] and Est3. Both proteins are essential for enzymatic activity in vivo. High-resolution NMR structures have been solved and interactions with oligonucleotide and protein binding partners have been studied. Obtained results provide new insights on the molecular mechanism of telomerase action. The work is supported by Russian Science Foundation grant 18-73-00068. References [1] O. A. Petrova, A. B. Mantsyzov, E. V. Rodina, S. V. Efimov, C. Hackenberg, J. Hakanpää, V. V. Klochkov, A. A. Lebedev, A. A. Chugunova, A. N. Malyavko, T. S. Zatsepin, A. V. Mishin, M. I. Zvereva, V. S. Lamzin, O. A. Dontsova, and V. I. Polshakov. Structure and function of the N-terminal domain of the yeast telomerase reverse transcriptase. Nucleic Acids Research, 46(3):1525–1540, 2018.