Telomerase

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An illustration to outline function of telomerase in extending telomere ends.

Telomerase is comprised of a protein and a RNA subunit. The protein is a Reverse transcriptase Enzyme called TERT which uses the RNA subunit TERC as a template for the addition of nucleotides to the overhang telomere ends of chromosome on the lagging strand of DNA to allow DNA replication to finish and the cell to continue with division[1]. Telomerase adds the repeating sequence TTAGGG to the end of the lagging strand[2]. The size of the RNA subunit varies between species depending on the telomere sequence needed. For example the Tetrahymena thermophila has 159 nucleotide bases in its RNA subunit, whereas budding yeast has an RNA subunit of 1167 nucleotides[3].

The activity of telomerase is vital for maintaining telomeres. In human somatic cells, the telomerase enzyme is switched off. This means that with every generation of cell division (successive cycles), the chromosome becomes progressively shorter as the telomeres are reduced on the lagging strand. As the lagging strand starts eating into the coding-DNA, the cell is no longer able to survive as genes start to be eaten in to due to no protection of their ends, known as 'senescence', meaning they stop expressing their proteins therefore causing the loss of cell functions eventually causing cell death. This allows the body to control the length of cell life.

In embryonic stem cells telomerase is activated, allowing them to avoid the end replication problem associated with many rounds of division[4], however it is inactivated during the process of differentiation.

In around 90% of cancers telomerase is reactivated[5], meaning that cells can divide indefinitely as the DNA does not become damaged. Telomerase plays an important part in ageing, and the prevention of ageing, as the telomerase enzyme is also switched on in germ line and stem cells, which allows them to divide continuously without any loss of DNA so the the cell life is longer.

Today, in science, we are exploring the many ways our understanding of the action of telomerase can help us prevent disease and ageing, through cell therapy and regenerative tissues, and also ovecome cancers through telomerase inhibition and the resulting shortening of its telomeres.

References

  1. Millar, S. (2009) 'Cell biology: the not-so-odd couple', Nature 460, 44-45 (2 July 2009)
  2. Lee J. Siegel. ARE TELOMERES THE KEY TO AGING AND CANCER? http://learn.genetics.utah.edu/content/begin/traits/telomeres/ Accessed 19/11/2013
  3. Masona, M. Schullera, A. and Skordalakesa, E. 'Telomerase structure function' PubMed
  4. Thomson JA, Itskovitz-Elder J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cells lines derived from human blastocysts. Science 282, 1145-1147
  5. Lackner DH, Karlseder J. C. elegans survivors without telomerase. Worm 2013; 2:e21073; http://dx.doi.org/10.4161/worm.21073
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