Inhibition of telomerase activity by reduction of poly(ADP-ribosyl)ation of TERT and TEP1/TP1 expression in HeLa cells with knocked down poly(ADP-ribose) polymerase-1 (PARP-1) gene.

Inhibitors of poly(ADP-ribose) polymerase have been shown to reduce the telomerase activity in cultured cells. To find out the specific member of the family, which participates in the regulation of telomerase activity, in the present investigation, we knocked down the gene by siRNA in HeLa cells and studied the telomerase activity. Reduction of expression of Pduanyu37-1 by siRNA increased cellular NAD(+) level and decreased general poly(ADP-ribosyl)ation of proteins. Telomerase activity decreased in cells with knocked down Pduanyu37-1 gene. Besides, we observed that telomerase reverse transcriptase (hTERT) was poly(ADP-ribosyl)ated in HeLa cells and such modification was decreased in cells with reduced Pduanyu37-1 expression. In addition, the expression of telomerase-associated protein 1 (TEP1/TP1) subunit of human telomerase holoenzyme reduced significantly in Pduanyu37-1 knock down HeLa cells. Thus, Pduanyu37-1 modulates the telomerase activity by altering poly(ADP-ribosyl)ation of TERT and/or the expression of TEP1/TP1.

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