Figure 2 | Oncogene

Figure 2

From: Telomerase is not an oncogene

Figure 2

Schematic of the telomere hypothesis of cellular aging and immortalization. The relationship between telomere length and time, measured typically in cell divisions, is shown for mortal (A) and immortal (B) human cells. In normal telomerase-negative mortal cells from many tissues there exists at least two telomere-dependent mortality phases (horizontal bars). Replicative senescence is is characterized by a checkpoint arrest likely triggered by a DNA damage response due to critical telomere loss or uncapping on one or a few chromosome ends. If cells lack this checkpoint, or suffer a transforming growth control mutation, they can continue to divide, losing telomeric DNA until the crisis phase characterized by major telomere dysfunction, genetic instability, and apoptosis. Although many cells lack detectable telomerase and lose telomeric DNA in a linear fashion with cell divisions (line a), certain cells from highly proliferative tissues have low or transiently activated levels of telomerase. These cells have a slower rate of telomere loss and an extended, but still finite lifespan (line b). The vertical bar represents non-telomeric checkpoint arrest mechanisms seen with many human and murine cells placed in culture (‘culture shock’), or when cells suffer non-lethal acute trauma or inappropriate growth conditions in vitro or in vivo. (B) illustrates telomere maintenance in: (a) immortal germline (reproductive) and embryonic stem cells, achieved by the normal constitutive expression of endogenous telomerase; (b) normal somatic cells immortalized by expression of ectopic (transduced) hTERT; and (c) tumor cells which have undergone growth control mutations and abnormal activation of endogenous telomerase. Based on Harley et al. (1990) and modified from Harley (1991)

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