Telomerase: Structure, functions, and activity regulation

M. I. Zvereva, D. M. Shcherbakova, O. A. Dontsova

Research output: Contribution to journalReview article

83 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1563-1583
Number of pages21
JournalBiochemistry (Moscow)
Volume75
Issue number13
DOIs
StatePublished - Dec 1 2010
Externally publishedYes

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Keywords

  • TERT
  • senescence
  • telomerase
  • telomerase RNA
  • telomerase activity
  • telomerase reaction cycle
  • telomerase regulators

ASJC Scopus subject areas

  • Biochemistry

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