Telomeric sequences

The use of alkali and alkaline earth group metal ions, especially those of sodium, potassium, magnesium, and calcium, for maintenance of electrolyte balance and for signaling and promotion of enzyme activity and protein function are not discussed in this text. Many of these ions, used for signaling purposes in the exciting area of neuroscience, are of great interest. In ribozymes, RNAs with catalytic activity, solvated magnesium ions stabilize complex secondary and tertiary molecular structure. Telomeres, sequences of DNA at the ends of chromosomes that are implicated in cell death or immortalization, require potassium ions for structural stabilization. 

Ambrus, A., Chen, D., Dai, J., Biabs, T., Jones, R.A. and Yang, D. (2006) Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution, Nucleic Acids Res., 34, 2723-2735. 

Telomerase is an enzyme in eukaryotes used to maintain the telomeres. It contains a short RNA template complementary to the DNA telomere sequence, as well as telomerase reverse transcriptase activity (hTRT). Telomerase is thus able to replace telomere sequences that would otherwise be lost during replication. Normally telomerase activity is present only in embryonic cells, germ (reproductive) cells, and stem cells, but not in somatic cells. 

In sequences such as d(TC5) and d(C3T) these C CH+ pairs are intercalated as is shown in Fig. 5-27. This intercalated DNA (I-DNA) may provide an alternative conformation for some telomeric sequences.281282 An I-DNA motif has also been identified in oligonucleotides from the DNA of human centromeres.283 The seemingly unusual forms of DNA described in this section may represent only a fraction of the naturally occurring DNA structures of biological significance. 

Greider, C. W., and Blackburn, E. H. (1989). A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature337, 331-337. 

Detection of DNA abasic site with light-up probes FISH to size the telomeric sequences... 

The solution structure of three-way junctions has been reported in an attempt to establish empirical stacking interactions of the helical arms. A variety of quadruplex structures have also been examined. Telomeric sequences... 

Thus, Telomerase is a reverse transcriptase with its own integral RNA template. It pairs with the telomere sequence and extends the ssDNA of the telomere. 

The telomerase RNA pairs with the telomere sequence and the enzyme then extends the telomere by RNA-templated DNA synthesis. DNA polymerase can then make (all but the end) double stranded. 

The natural occurrence of G-quadmplex in human telomeric sequences remains unproven, although a recent report provides convincing evidence of their occurrence in Stylonychia lemnae telomeres (80). Nevertheless, the existence of... 

The chromosomes of eukaryotes are linear, and replication of the free ends of these linear DNA molecules presents particular problems. The sequencing of the ends of chromosomes revealed that they consist of telomeres, hundreds of tandem repeats of a hexanucleotide sequence, which in all vertebrates is d(TTAGGG). These G-rich telomeric sequences can fold into a G-quadruplex, a DNA secondary structure consisting of stacked G-tetrad planes, or G-quartets (Figure 9.18), connected by a network of Hoogsteen hydrogen bonds the cavity in the centre... 

R658 M. Katahira, Structure of Telomere-Sequence DNA/RNA-Binding Protein, hnRNP DO, and Transformation of DNA/RNA Quadruplex to a Single Strand by hnRNP DO , Seibutsu Butsuri, 2000,40, 326... 

Yu, G.L., Bradley, J.D., Attardi, L. D., and Blackburn, E.H. (1990). fra vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344, 126-132. 

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