Telomere elongation

A human Estl ortholog, ESTIA, is associated with most or all active telomerase in human cell extracts and is involved, either directly or indirectly, in chromosome end-capping and telomere elongation [24, 25]. Another yeast subunit, Est3p, is similarly important for activity in vivo but not in vitro, with its specific function unknown. 

Under other conditions, human POTl can stimulate telomere elongation... 

Lundblad, V., and Szostak, J.W. (1989). A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633-643. 

Smith S, de Lange T. Tankyrase promotes telomere elongation in human cells. Curr Biol 2000 10(20) 1299-302. 

Agarwal, S., Loh, Y. H., McLougldin, E. M. et al. 2010. Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients. Nature 464 292-6. 

Telomerase is a reverse transcriptase that copies the DNA sequence of the telomeric repeats from a small guide RNA that is part of the enzyme. Tire first telomerase studied was the relatively abundant enzyme from Tetrahymena. It contains a 159-nucleotide RNA with the sequence 5 -CAACCCCAA-3 at positions 43-51. This sequence is complementary to the 5 -TTGGGG-3 repeat sequence of the Tetrahymena telomeres.450 451 A 127-kDa human protein contains a similar guide RNA with the sequence 5 -CUAACCCUACC-3, which is complementary to the human telomere repeat sequence as is illustrated in Fig. 27-21.452-454 Telomerases455 456 evidently allow the cell to elongate the telomere 5 -ends using the... 

Agents that stabilize G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalyzed by telomerase or the telomerase-independent mechanism, and could therefore act as antitumor agents [26-30]. 

A. G. Bodnar, M. Ouellette, M. Frolkis, S. E. Holt, C. P. Chiu, G. B. Morin, etal. Extension of life-span by introduction of telomerase into normal human cells [see comments]. Science, 279 (5349), 349-352,1998. Also H. Vaziri and S. Benchimol. Reconstitution of telometase activity in normal human cells leads to elongation of telomeres and extended replicative life span. CurrBid, 8 (5), 279-282, 1998. 

Telomerase A ribonucleoprotein complex that catalyzes the synthesis of DNA at the ends of chromosomes and confers replicative immortality to cells. It is considered to be important in the growth of cancer cells and is a therapeutic target. See Blackburn, E.H., Greider, C.W., Henderson, E. et al.. Recognition and elongation of telomeres by telomerase. Genome 31, 553-560, 1989 Lamond, A.L, Tetrahymena telomerase contains an internal RNA... 

Figure 12.9 (A) Schematic illustration of overall assay design for ZnO NR-based telomeric repeat elongation assays. TS is an oligonucleotide whose sequence is recognized by telomerase. (B) Fluorescence panel obtained from positive (1) versus negative (2) samples after performing telomeric repeat elongation assays on ZnO NR stripe platforms.

Dorfman, A., Parajuli, O., Kumar, N., and Hahm, J. (2008). Novel telomeric repeat elongation assay performed on ZnO nanorod array supports. J. Nanosci. Nanotech. 8 410-415. 

Telomerase is a ribonucleoprotein complex that exists in eukaryotic cells for the apparently sole purpose of synthesizing telomeric DNA, which consists of tandemly repeated sequences that contain clusters of G-residues and forms the ends of chromosomes. Telomerase comprises two essential core components, a protein subunit that has reverse transcriptase (RT) activity and an RNA sequence (hTR) that contains clusters of C-residues and serves as the template substrate for the RT (6). The G-rich DNA and C-rich RNA anneal to form a partial duplex with DNA as the primer. RT-mediated polymerization of dGTP and other complementary triphosphate substrates produces a DNA terminus that has been extended by around six nucleotides. The new end can become a substrate for either another round of telomerase-mediated elongation or primase/polymerase-mediated lagging-strand synthesis. 

Applications of cyclised oligonucleotides are varied. They have been used to produce artificial human telomeres by rolling circle DNA synthesis/as inhibitors of viral replication in influenza virus and as structural motifs for quadruplex formation.A further form of cyclic oligonucleotide figures in a recently described method in which a self-complementary oligonucleotide, e.g., a hairpin structure, is denatured and allowed to re-anneal in the presence of circular DNA such as a plasmid (7). The effect is that the short oligonucleotide traps the plasmid in what has been termed a padlock. Such structures have been successfully used to inhibit transcription elongation reactions based on triple helix formation of the padlock structure. 

The TRAP (telomeric repeat amplification protocol) assay is a widely used method for detection of telomerase activity. This technique measures the telomerase activity present in cell extracts. Briefly, cellular extract containing telomerase activity is incubated with a telomeric substrate (a short strand of DNA onto which the telomerase wiU. attach the telomeric repeats) followed by polymerase chain reaction (PCR) amplification of the elongated telomere. Detection of the PCR product is by a number of methods, including gel electrophoresis, radiometric detection, ELISA, and real-time PCR detection. ... 

Verbascoside is able to inhibit another enzyme related to tumor cells, the telomerase [85]. The tumoral cells express this enzyme that elongates the 3 ends of telomere [133]. Telomere shortening and telomerase activity have been detected in almost all human tumors but not in normal somatic tissues [133, 134], Zhang and cols, [85] showed that the telomerase inhibition by verbascoside may involve telomere-lenght regulation. 

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