Telomeric plasmid induces human cancer cell dysfunction depending on ATM activity.

Telomeres are essential for chromosome stability and the regulation of the replicative life-span of somatic cells. Many studies showed that exogenous telomeric repeats could activate p53 protein. It is not known how cell dysfunction is induced by telomeric plasmids. A covalent closed circular (ccc) double-stranded plasmid containing (TTAGGG)(96) repeats (pRST5) was transiently transfected into the human gastric cancer MGC-803 cells. We first confirmed that the cell viabilities decreased by 27%, cell senescence increased by 62% and G2/M cycle arrested in pRST5 plasmid transfected cells. Compared to control groups, cells transfected with telomeric plasmids showed an ATM-dependent increasing of p53, TRF1, and TRF2 expression. Furthermore, telomere dysfunction-induced foci (TIF) were observed. In conclusion, telomeric plasmids can elicit endogenous telomere dysfunction and induce cell senescence by activating ATM-p53 pathway. Copyright 2010 John Wiley & Sons, Ltd.