Telomeres – friend or foe?

Telomeres are repeated sections of DNA found at the end of our chromosomes. In humans, the DNA-base sequence TTAGGG is repeated many times to make up each telomere. These telomeres are very important sections of our DNA – not only do they prevent our chromosomes from sticking to each other, but they protect important sections of DNA from being lost during replication [1]. Each time a chromosome is replicated, multiple bases are lost from the ends, but these lost bases are merely the telomeric repeats, so no genes are damaged. However, when a telomere becomes very short, the ‘crisis point’, it produces a signal that stops cell division from occurring. The cell then enters a phase called senescence, where it functions less efficiently and ultimately dies [2].

Therefore, to prevent a cell from becoming senescent, there must be a way of maintaining telomere length. This comes in the form of the enzyme telomerase. Telomerase contains an RNA molecule attached to the nucleotide template to construct telomeric subunits (TTAGGG). Telomerase places its RNA molecule in line with the tip of a DNA strand. The enzyme then adds DNA nucleotides to form a telomeric subunit, before sliding down to the new tip of the strand and repeating this process. This means that, when bases are lost from each of the ends of chromosomes during replication, it is only the bases added by telomerase. Therefore, the daughter strands are no shorter than the parents [2].

Most adult somatic cells do not show any detectable telomerase activity, meaning they can divide only a finite number of times. This is relatively insignificant, because most cells can replicate around 90 times before becoming senescent, which is more times than would be needed for a normal human life span. The lack of telomerase activity in somatic cells however, is significant in avoiding cancer. Usually, cancer cells only manufacture telomerase due to a mutation [2]. This causes the telomeres to be maintained, giving the cells immortality. This means the cancer cells may continue to proliferate forming tumours – something they wouldn’t have been able to do without telomerase [2].

Telomerase activity is high in spermatogonia (a type of stem cell which can divide to produce sperm cells), which causes sperm telomere length to increase over time. This is important because sperm telomeres play a vital role in fertilisation after meeting an egg cell. Conversely, egg cells do not show any telomerase activity. Egg cell telomeres are shorter than telomeres of somatic and sperm cells, and get even shorter with time. This is important because the older a female is, the more dangerous pregnancy can be for both mother and child [3].

Another interesting discrepancy is that while embryonic stem cells have high levels of telomerase activity, and fully maintain their telomeres, adult stem cells have (although still having detectable levels of telomerase), do not have enough to fully maintain their telomeres. This can be explained by the fact that embryonic stem cells need to divide many more times than an adult stem cell. An adult stem cell may need to divide for example, to repair an organ or to replace dead cells, but this is small compared to making up a full organism [4].

In summary, the level of telomerase activity within a cell is directly related to its function. The lack of telomerase in most somatic cells is likely to be an anti-cancer mechanism, and the few cells with high telomerase activity only have this because it is required for their function.

 

Chas Alexander Smith

 

References

  1. Papachristodoulou, DK, Snape, A, Elliott, WH and Elliott, DC; “Biochemistry and molecular biology”; 2014; 5th edition; Oxford; 361-363
  2. Greider, CW and Blackburn EH; “Telomeres, telomerase and cancer”; 1996; Sci Am 274(2) 92-97
  3. Kalmbach, KH, Antunes, DMF, Dracxler, RC, et al.; “Telomeres and human reproduction. Fertility and sterilitiy”; 2013; Fertnstert 99(1)
  4. Shay, JW and Wright WE; “Telomeres and telomerase in normal and cancer stem cells”; 2010; FEBS Lett 584(17) 3819-3825

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