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Review
. 2013 Dec;162(6):333-42.
doi: 10.1016/j.trsl.2013.08.009. Epub 2013 Sep 23.

Telomere biology and translational research

Philip J Mason  1 , Nieves Perdigones
Affiliations
Review

Telomere biology and translational research

Philip J Mason et al. Transl Res. 2013 Dec.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1. Conservation of telomeres
When circular DNA from yeast is cut with a restriction enzyme, the linearized DNA becomes very unstable. However, if telomeres from Tetrahymena are added, the linearized plasmid becomes stable (10). This demonstrates that telomeres are very conserved between species. In order to clone the yeast telomeres Szostak cut the end of the linearize DNA and added different yeast sequences to select for those that stabilzed it (8).
Figure 2
Figure 2. Identification of telomerase
As shown in the gel diagram, the oligonucleotide (TTGGGG)4, the telomere sequence for Tetrahymena, was extended by telomerase in a cell free extract (10). The extension of yeast telomeres with the sequence TGGG is shifted one base showing that a G must be added before extension takes place. Telomerase activity is blocked by the complimentary sequence of Tetrahymena telomeres CCCCAA.
Figure 3
Figure 3. Dynamics of telomere length in germ, stem, somatic and tumor cells
Telomere length in germ cells is stable, while it decreases slightly in stem cells with time. Telomerase is expressed in both cell types. However, telomerase is not expressed in normal somatic cells, and telomere length decreases with each replication cycle. When telomeres get critically short, normal cells go into senescence. However, mutations can occur that enable the cells to continue dividing and telomeres get even shorter. They enter a crisis. Crisis is characterized by cell death and concomitant cytogenetic abnormalities produced by chromosome fusion/breakage cycles. Telomeric crisis produces significant chromosomal instability, a hallmark of human cancer, and may increase the occurrence of genetic alterations that would favor neoplastic transformation. If the telomerase enzyme is activated, these cells can grow to form a tumor (–18).
Figure 4
Figure 4. Telomerase and telomeres
Telomeres are nucleoprotein complexes at the end of chromosomes that protect and stabilise them. The T-loop conformation of the telomeres are resolved by the protein RTEL and others before replication. Then, members of the shelterin complex recruit the telomerase complex to the telomere region. Here, the telomerase works uses its integral RNA as a template to elongate telomeres. The CST complex binds to the extended telomeres and supresses telomerase access (55). The CST complex also promotes fill-in synthesis of the C-strand stimulating DNA polymerase α-primase. * mutations in the genes encoding these proteins (or RNA in the case of TERC) have been linked to Dyskeratosis congenita (26).
Figure 5
Figure 5. Telomere based therapeutic approaches proposed to treat cancer
These possible routes to cancer therapy are based on the observation that telomerase is expressed in cancer cells but not in other somatic cells (77).
See this image and copyright information in PMC

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