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Abstract
The enzymatic activity of telomerase counters erosion of telomeric DNA that occurs as a biochemical consequence during replication. This primary function of telomerase resolves the ‘end-replication problem’ and prevents telomere dysfunction and replicative senescence ensuring cellular immortality. The vast majority of human cells are devoid of telomerase activity but reactivation of telomerase occurs in more than 80% of human cancers. Moreover, telomerase activity is a pre-requisite of sustained organ maintenance under physiological hyper-proliferative conditions such as liver regeneration and for the proliferation of activated B- and T- cells. Increasing evidence indicates at telomere length independent functions of telomerase, including DNA-damage repair, mitochondrial function and stem cell activity. Mechanisms of how telomerase can fulfill such diverse functions remain yet to be elucidated. Our recent findings showing that telomerase activates ribosomal biogenesis under oncogenic and regenerative conditions can shed a light to some of these questions.
Highlights
Accumulating evidence indicates that telomerase holoenzyme or its components TERT and TERC may exert some fundamental biological functions independent of their role in telomere maintenance, including DNA-damage response, cell survival and apoptosis [26,27,28,29,30,31,32]
As ribosomal biogenesis is vital for growth and proliferation [53] and telomerase stimulates cellular proliferation, we asked if telomerase exerts this effect through stimulating rDNA transcription
Strong telomerase activity is detectable in resting mouse liver and TERT-immortilized, non-transformed human primary cells but no impact on rDNA transcription or polymerase I (Pol I) association was observed in these samples
Summary
Accumulating evidence indicates that telomerase holoenzyme or its components TERT (the catalytic subunit of telomerase) and TERC (the telomerase RNA component) may exert some fundamental biological functions independent of their role in telomere maintenance, including DNA-damage response, cell survival and apoptosis [26,27,28,29,30,31,32]. Increasing evidence indicates at telomere length independent functions of telomerase, including DNA-damage repair, mitochondrial function and stem cell activity.
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