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The Telomerase Apocrypha

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Posted 28 April 2006 - 07:01 AM

Telomerase is known as an enzyme that catalyses the repair of chromosome ends following each cell division. Its expression is constitutively silenced in non-stem type cells which leads to chromosomal instability and senescence after approximately 50 cell divisions in humans. Cell lines in the lab have been "immortalised" (they can divide indefinitely) by introduction of telomerase and since most cancer cells - which can be described as rebel stem cells - express telomerase, a putative cancer treatment would be targeting cells that are innapropriately expressing telomerase (which is what one of the SENS strategies, WILT, seeks to do).

However, telomerase has also been more recently shown to be associated with DNA repair mechanisms and with the regulation of chromatin configuration. Aside from casting a shadow on the WILT solution, it highlights that the function of this gene is more complex and critical to cell physiology than the original single dimension in which it had been cast.

Now to throw an even greater spanner in the works, telomerase has been found to have a mitochondrial localisation sequence which directs the enzyme to these organelles. But since mitochondrial DNA is circular, telomerase can provide no telomere maintenance function there. As if that was not strange enough, the study below reports that the presence of telomerase in mitochondria mediates oxidative-type DNA damage to the mitochondrial genome which results in apoptosis. You read correctly - mediates.

Now why on earth would a mechanism exist that couples chromosomal maintenance with mitochondrial damage and cell apoptosis and how is this mechanism reconciled in terms of stem, cancer and other immortalised cells? As the authors suggest, the purpose could be to increase quality control in more rapidly dividing cells by making them more sensitive to damage.

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