Solo disponible en BuenasTareas
  • Páginas : 75 (18695 palabras )
  • Descarga(s) : 0
  • Publicado : 29 de agosto de 2012
Leer documento completo
Vista previa del texto
ISSN 0006 2979, Biochemistry (Moscow), 2010, Vol. 75, No. 13, pp. 1563 1583. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © M. I. Zvereva, D. M. Shcherbakova, O. A. Dontsova, 2010, published in Uspekhi Biologicheskoi Khimii, 2010, Vol. 50, pp. 155 202.


Telomerase: Structure, Functions, and Activity Regulation
M. I. Zvereva*, D. M. Shcherbakova, and O. A. DontsovaFaculty of Chemistry, Lomonosov Moscow State University, 119999 Moscow, Russia; E mail:
Received January 25, 2010
Revision received May 1, 2010
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 cellsprolifer
ation potential is strictly limited and senescence follows approximately 50 70 cell divisions. In most tumor cells, on the con
trary, 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 ofchromosomes; 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 cellcycle 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 elongationthat 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 organ
isms. Problems of telomerase activity measurement and modulation by enzyme inhibitors or activators are considered as
DOI: 10.1134/S0006297910130055
Key words: telomerase, senescence, TERT, telomerase RNA,telomerase reaction cycle, telomerase activity, telomerase reg

Telomeres are DNA–protein structures that are
localized at the ends of eukaryotic chromosomes. They
protect the linear ends of eukaryotic chromosomes
against degradation and fusion, thus maintaining genome
stability. The cell replication apparatus is not able to pro
vide for complete replication of chromosome ends;also,
telomeres are subject to the action of nucleases and other
destructive factors. As a result, telomeres shorten during
each cell division (Fig. 1). In most organisms the main
mechanism of telomere length maintenance is comple
tion of DNA telomere repeats by telomerase [1]. This
enzyme elongates the chromosome 3′ end, whereas the
Abbreviations: CTE, C terminal TERT domain (C terminalextension); IFD, TERT domain (insertion in fingers domain);
Pif1p, helicase of Saccharomyces cerevisiae; TER, telomerase
RNA; TERRA, RNA transcribed from telomeric DNA (telom
eric repeat containing RNA); TERT, telomerase reverse tran
scriptase; TLC1 RNA, telomerase RNA of Saccharomyces cere
visiae; TWJ, Y like structural element of RNA (three way junc
* To whom correspondence should beaddressed.

complementary strand is completed by DNA polymeras
Telomerase is a ribonucleoprotein complex [2]. The
core enzyme includes telomerase reverse transcriptase
and telomerase RNA containing a template site for DNA
elongation. The telomerase complex also contains a num
ber of auxiliary components that provide for functioning
of telomerase in vivo. Some of these components are...
tracking img