Telomerase and its Biological Function

Telomeres
Telomeres are a repetitive sequence of DNA at the ends of our chromosomes. They serve to protect the ends of the chromosomes from being frayed or tangled. Additionally they’re important in the context of the end replication problem.

Telomeres and Cell Mortality
Due to the nature of DNA replication of the lagging strand, every round of replication leads to the ends of the chromosomes shortening over time. This process is termed the end replication problem. The telomeres have a repetitive sequence of DNA that can act as a ‘buffer’ to ensure the shortening of the ends of the chromosomes doesn’t damage important genes. In that way, the length telomeres act as a sort of internal limit on cell replication, where a cell will be unable to replicate infinitely as their telomeres will eventually be depleted (1).

Figure 1: An animation depicting the shortening of the telomeres over multiple replicative cycles.

However, this cell ‘mortality’ is mainly present in somatic cells. Germline and stem cells on the other hand don’t run into this issue, as their telomeres don’t deplete. This can be attributed to the enzyme telomerase (2).

Telomerase
Telomerase is a ribonucleoprotein which is capable of extending telomeres. It is composed of two subunits: the TERC RNA component and the TERT reverse transcriptase component. In most somatic cells, it is not expressed. On the other hand in germline and stem cells, telomerase is expressed, and is the reason that those cells in particular do not see depletion of their telomeres (2).

Cancer
One ubiquitous feature of cancer cells is their rapid replication. If they were the same as somatic cells, this rapid replication would eventually be limited by depletion of their telomeres. However this is not observed, because cancer cells also display telomerase activity in order to overcome this issue (3). As a result, telomerase and proteins that interact with it have a lot of potential as targets for cancer therapeutics.

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References

1.
Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB. Telomere end-replication problem and cell aging. Journal of molecular biology. 1992;225(4):951–60.
2.
Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW. Telomerase activity in human germline and embryonic tissues and cells. Developmental genetics. 1996;18(2):173–9.
3.
Shay JW, Zou Y, Hiyama E, Wright WE. Telomerase and cancer. Human molecular genetics. 2001;10(7):677–85.