Telomerase: Structure, functions, and activity regulation

被引:170
作者
Zvereva, M. I. [1 ]
Shcherbakova, D. M. [1 ]
Dontsova, O. A. [1 ]
机构
[1] Moscow MV Lomonosov State Univ, Fac Chem, Moscow 119999, Russia
基金
俄罗斯基础研究基金会;
关键词
telomerase; senescence; TERT; telomerase RNA; telomerase reaction cycle; telomerase activity; telomerase regulators; REPEAT ADDITION PROCESSIVITY; SACCHAROMYCES-CEREVISIAE TELOMERASE; RNA-BINDING DOMAIN; STEM-LOOP IV; RECOMBINANT TETRAHYMENA TELOMERASE; TEMPLATE BOUNDARY DEFINITION; HIV-1; REVERSE-TRANSCRIPTASE; SMALL NUCLEOLAR RNPS; SINGLE-STRANDED-DNA; N-TERMINAL REGION;
D O I
10.1134/S0006297910130055
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1563 / 1583
页数:21
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