Extended Data Fig. 7: Disease related mutations and telomerase activity assays.

a-e Locations of disease related mutations. a, Back view of TEN–TRAP–TPP1 interface as in Extended Data Fig. 6. Residue positions with disease mutations in TEN, TRAP, and TPP1 (Supplementary Table 1^13,71,72) are shown as yellow (interface) and gray (non-interface) spheres. b, c, Zoomed-in views of intra-(b) and inter-(c) domain interactions from residues related to disease mutations that may disrupt TPP1–TERT interaction indirectly. d–i Telomerase activity assays for TERT variants with residue substitutions at the interface with TPP1. d, Telomerase activity assays corresponding to Fig. 2g. Gel is a representative from 3 independent experiments. The number of telomeric repeats added to primer are indicated at left, and number of nucleotides are indicated at right. RC, recovery control. e, f, Relative activity (e) and RAP (f) normalized to TERT WT without TPP1. Plotted values are mean ± s.d. from n = 3 biologically independent experiments. g, Telomerase activity assays without and with TPP1–POT1. Gel is a representative from 2 independent experiments. h, i, Relative activity (h) and RAP (i) normalized to TERT WT without TPP1-POT1. Open circles are values from n = 2 biologically independent experiments.