Fig. 3: Terminal 6-thio-dG bases impair telomerase RAP but not telomerase binding. | Nature Communications

Fig. 3: Terminal 6-thio-dG bases impair telomerase RAP but not telomerase binding.

From: Therapeutic 6-thio-deoxyguanosine inhibits telomere elongation in cancer cells by inducing a non-productive stalled telomerase complex

Fig. 3

a Telomerase reactions conducted with 6-thio-dG at different positions on the telomeric substrate primer. P marks the unextended 18-mer primer, and numbers indicate the number of added repeats. Lane number corresponds to primer sequence in panel (c). b Cartoons of telomeric primer (gray) with 6-thio-dG (red), telomerase RNA template (purple), and incoming dNTP (green). Created in BioRender. Sanford, S. (2025) https://BioRender.com/brfbsrx. c Quantitation of percent primer extension. Data represent the mean ± s.d. from three independent experiments. Statistical significance was determined by one-way ANOVA (**P = 0.0037; ****P < 0.0001). Sequence of 3’ terminal telomeric repeat in the 18 mer primer following (GGTTAG)2 is shown on the Y axis (see Supplementary Table 1). Purple G’s indicate 6-thio-dG modification. d Binding reactions were conducted with 2.5 nM fluorescein labeled telomere substrate (30 mer) with a 3’ terminal dG or 6-thio-dG (blue) (see Supplementary Table 1) and 1–20 nM Halo-telomerase conjugated with JF-635 dye (red), for 30 min at room temperature, and separated by EMSA to visualize telomerase-bound substrate (pink). e Quantification of % DNA bound versus estimated Halo-telomerase concentration. Data represent the mean ± s.d. from three independent experiments. Source data are provided as a Source Data file.

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