Addition of Telomerase to Somatic Cells
Telomerase is an enzyme that is able to regenerate telomeres. In humans, it is found in some tissues, such as male germ cells, activated lymphocytes, and certain types of stem cell populations. If present in somatic cells, it can turn them cancerous following mutation. Telomere shortening is one of the factors which contribute to aging so it is worthwhile to look into such an addition to develop anti-aging treatments.
Telomerase is a reverse transcriptase enzyme with its own RNA template. This makes it very similar to DNA viruses with the notable exception of capsids. Such similarities could be used to establish the idea that viruses may have fused with the cells of other organisms to give rise to telomerase in the course of evolution from the RNA world.
Telomeres are repeating sequences of nucleotides at the end of chromosomes which do not code for any proteins. This sequence has been identified to be "TTAGGC". Now, DNA polymerase is not capable of replicating the chromosome along its entire length. Hence every time DNA replications are undergone, the ends of chromosomes will be left out. Telomeres are extra sequences at those very ends so they can be lost instead of other vital protein-coding sequences. Leonard Hayflick demonstrated that a normal human fetal cell population will divide between 40 and 60 times in cell culture before entering a senescence phase. It occurs because each time a cell undergoes mitosis, the telomeres on the ends of each chromosome shorten slightly. Cell division will cease once telomeres shorten to a critical length. Hayflick interpreted his discovery to be aging at the cellular level.
The molecular composition of the human telomerase complex was determined by Scott Cohen and his team at the Children's Medical Research Institute (Sydney Australia) and consists of two molecules each of human telomerase reverse transcriptase (TERT), telomerase RNA (TR or TERC), and dyskerin (DKC1). That was the whole complex but the parts of telomerase of key interest: one is the functional RNA component, hTERC which serves as a template for telomeric DNA synthesis: the other is a catalytic protein, hTERT with reverse transcriptase activity .The genes of telomerase subunits, which include TERT, TERC, DKC1 and TEP1, are located on different chromosomes. The human TERT gene (hTERT) is translated into a protein of 1132 amino acids. TERT polypeptide folds with (and carries) TERC, a non-coding RNA (451 nucleotides long).
Telomerase Gene in Somatic Cells
Among the core components of human telomerase, only the catalytic component hTERT seems to be the limiting determinant of telomerase activity, as other components are undergo constitutive regulation. It is transcriptionally repressed in many normal cells.Substantial experimental data demonstrate that the transcriptional regulation of hTERT expression represents the primary and rate-limiting step in the activation of telomerase activity in most cells. It has been proposed that the lack of telomerase activity in most somatic human cells is due to transcriptional repression of the hTERT gene. Consistent with this hypothesis, cell fusions between normal somatic cells and some telomerase-positive immortal cells result in repression of telomerase activity . Importantly, microcell-mediated transfer of specific human chromosomes into cancer cells results in repression of hTERT expression and downregulation of telomerase activity . These observations indicate that normal cells express functional transcriptional repressors of hTERT .
Telomerase Activity in Somatic Cells
Most types of normal human somatic cells, however, are telomerase negative and have a limited replicative capacity . When this limit is reached, which depends on cell type and origin, cells will permanently cease proliferating. It has been suggested that senescence could function as a tumor suppressor mechanism to prevent the accumulation of multiple oncogenic mutations .
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