Telomere Maintenance Mechanisms in Mammals 21 Telomerase

The main mechanism for telomere elongation is the enzyme telomerase, which consists of a reverse transcriptase subunit (TERT) that is able to synthesize telomeric repeats de novo and add them to chromosome ends using an associated RNA molecule (TERC) as a template (Chan and Blackburn 2002; see also Dillin and Karlseder, this volume). The attrition of telomeric DNA that takes place during ageing is likely to result from limiting amounts of telomerase activity in the adult organism, which cannot compensate for the progressive telomere shortening that occurs as cells divide during tissue regeneration (Collins and Mitchell 2002, Blasco et al. 2005; see also Allsopp, this volume). In this regard, telomerase has been found to be crucial for stem cell function and proliferative potential (See Du et al., this volume, and Zimmerman and Martens, this volume), which anticipates its known role in cancer and ageing (See Rudolph, this volume). On one hand, short telomeres due to telomerase deficiency result in impaired stem cell functionality, defective tissue regeneration, and decreased tumorigenesis (Flores et al. 2005), while telomerase overexpression has opposite effects (Flores et al. 2005, Sarin et al. 2005). These findings suggest that telomere length and telomerase activity are important determinants of stem cell behavior and that it is in this context that they may influence cancer and ageing (see Gutierrez and Ju, this volume).

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