DNA damage transiently increases TRF2 mRNA expression and telomerase activity.
Telomerase activity transiently increases when HL60 cells are treated with the topoisomerase II inhibitor etoposide. A quantitative assessment revealed that telomerase is activated by etoposide treatment in a number of cell lines and that the increase is reversible after withdrawal of etoposide from the cell culture. Telomerase activation correlated with the occurrence of DNA damage but not with cell cycle arrest. We did not detect any transcriptional upregulation of hTERT mRNA, suggesting a post-transcriptional mechanism of telomerase activation. Furthermore, the mRNA expression of the telomere binding protein TRF2 was upregulated early and reversibly after etoposide treatment. TRF1 mRNA expression levels were unchanged after DNA damage, but increased when the cells accumulated in the G2/M phase. The data show that the telosome reacts after DNA damage by upregulating telomerase activity and TRF2 expression in malignant cells. It has previously been shown that overexpression of TRF2 can repress senescence signals arising from critically shortened telomeres. We show here that TRF2 is upregulated by undirected DNA damage that also affects the telomeric DNA. These data suggest that upregulation of telomerase activity and TRF2 expression might act as antiapoptotic mechanisms in the DNA-damage response of malignant cells.
D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D020552:Comet Assay; D004249:DNA Damage / Q000235:genetics*; D017931:DNA Primers; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics*; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D035341:Telomeric Repeat Binding Protein 2; D005047:Etoposide; D019098:Telomerase