Telomerase: Structure,functions, and activity regulation |
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Authors: | M I Zvereva D M Shcherbakova O A Dontsova |
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Institution: | Faculty of Chemistry, Lomonosov Moscow State University, Russia. zvereva@genebee.msu.ru |
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Abstract: | Telomerase is the enzyme responsible for maintenance of the length of telomeres by addition of guanine-rich repetitive sequences.
Telomerase activity is exhibited in gametes and stem and tumor cells. In human somatic cells proliferation potential is strictly
limited and senescence follows approximately 50–70 cell divisions. In most tumor cells, on the contrary, replication potential
is unlimited. The key role in this process of the system of the telomere length maintenance with involvement of telomerase
is still poorly studied. No doubt, DNA polymerase is not capable to completely copy DNA at the very ends of chromosomes; therefore,
approximately 50 nucleotides are lost during each cell cycle, which results in gradual telomere length shortening. Critically
short telomeres cause senescence, following crisis, and cell death. However, in tumor cells the system of telomere length
maintenance is activated. Besides catalytic telomere elongation, independent telomerase functions can be also involved in
cell cycle regulation. Inhibition of the telomerase catalytic function and resulting cessation of telomere length maintenance
will help in restriction of tumor cell replication potential. On the other hand, formation of temporarily active enzyme via
its intracellular activation or due to stimulation of expression of telomerase components will result in telomerase activation
and telomere elongation that can be used for correction of degenerative changes. Data on telomerase structure and function
are summarized in this review, and they are compared for evolutionarily remote organisms. Problems of telomerase activity
measurement and modulation by enzyme inhibitors or activators are considered as well. |
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