Effect of telomerase and telomeres inhibitors on a linear and a circular HAC mis-segregation rate. A, Effect of the telomerase inhibitor GRN163L, that directly binds with high affinity and specificity to the RNA component of telomerase (hTERT), on the stability of a linear and a circular HAC. HT1080 cells containing either a linear or a circular HAC were treated by GRN163L at concentrations of 1 μM, 10 μM or 50 μM for 3 days. A specific concentration-dependent destabilization of the linear HAC was observed. B, Effect of telomerase and telomeres inhibitors, 6-Thio-dG, BIBR1532, GRN163L and MST-312, on a linear versus a circular HAC mis-segregation rate. HT1080 cells containing either a linear or a circular HAC were treated with the compounds at the concentrations corresponding to their LC50 (Supplementary Table S2) overnight. MST-312 was the strongest CIN inducer (approximately 40-fold increase of loss rate of a linear HAC). C, Effect of 19 G-Quadruplex ligands that may recognize telomere repeats on a linear and a circular HAC mis-segregation rate. The highest rate of the linear HAC loss was observed after treatment by Cu-ttpy and Pt-ttpy (almost 70- and 90-fold increase compared to the control, correspondingly). *stands for <0.001 (done by t-test). ** stands for p<0.005 (done by t-test).