Figure 1. Biochemical activity of telomerase. The enzyme telomerase is made of two essential subunits, human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR). The hTR RNA contains a short sequence, complementary to that of the telomeric repeats (5¢-CUAACCCUAA-3¢), which the enzyme uses as a template. As the enzyme associates with the telomeres, this sequence hybridizes with the 30 overhang that caps all telomeres. The protein hTERT, acting as a reverse transcriptase, then uses the telomere as a primer and hTR as a template to synthesize a six-base telomeric repeat. The enzyme is highly processive and can add many repeats to the same DNA substrate through cycles of synthesis and translocation.

Figure 2. Mortality stages 1 and 2. Most somatic human cells lack telomerase, and as a consequence, shorten their telomeres at each round of cell divisions. When the shortest telomere reaches a threshold size, Mortality Stage 1 (M1 or Senescence) is triggered. The cell cycle arrest that characterizes M1 is maintained by the activities of p53 and RB, and can therefore be bypassed by the loss of these tumour suppressors. Cells that have overcome M1 continue to shorten their telomeres as they divide, until the induction of Mortality stage 2 (M2 or crisis). M2 is characterized by massive cell death and is due to terminal telomere shortening. Rare cells can escape M2 to give rise to immortal clones, but only after telomeres have become stabilized through either telomerase (hTERT) expression or activation of the ALT pathway.