Telomerase Maintains Telomere Structure in Normal Human Cells

Abstract

In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3' single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence.

Induction of bovine articular chondrocyte senescence with oxidized low‐density lipoprotein through lectin‐like oxidized low‐density lipoprotein receptor 1

“…This suggests that the telomerase activity in BACs is upregulated during cell expansion. This result is consistent with the findings of previous reports on the telomerase activity of cultured chondrocytes (46,47) and proliferating somatic cells (48,49). Taken together, these data indicate that the telomerase activity in proliferating and cloning chondrocytes in the early phase of OA is up-regulated and plays an important role in tissue repair by postponing cell senescence and maintaining cell function.…”

Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation

“…The Human Umbilical Vein Endothelial Cells [13]. The establishment of a stable clone with downregulated psoriasin expression was made by transfecting MCF10A with shRNA directed against human psoriasin, as previously described [14][15].…”

Telomerase promotes efficient cell cycle kinetics and confers growth advantage to telomerase-negative transformed human cells

“…Low levels of endogenous telomerase expression were found in primary fibroblasts, but this activity did not support stable telomere maintenance. However, when this endogenous telomerase expression was disrupted by RNA interference, an early exit from the cell cycle into quiescent senescence was observed (Masutomi et al, 2003). Knocking down the low-level endogenous TERT expression in primary fibroblasts affected the overall configuration of chromatin, increased fibroblast sensitivity to ionizing radiation and resulted in a diminished capacity to repair genomic DNA damaged by exposure to ionizing radiation.…”