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.
Guo
Xiao-Fei
XF
Institute of Biophysics, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Chaoyang District, Beijing, PR China.
Cao
En-Hua
EH
D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016195:G2 Phase; D006801:Humans; D010957:Plasmids / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D013274:Stomach Neoplasms / Q000378:metabolism; D016615:Telomere / Q000737:chemistry* / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases