Figure 2. Somatic mutations relative to protein functional domains and POT1 functional studies.

Schema showing somatic mutations relative to mutant protein/gene with conserved domains drawn for (A) TP53, (B) the TERT promoter, (C) shelterin components, and (D) nuclear RNA exosome components, respectively. The key denotes the group in which the mutation was identified, with open circle referring to controls, black circles to patients with short telomere syndromes without MDS/AML, and red circles to patients with short telomere syndromes with MDS/AML. (E) Electrophoretic mobility shift assay (EMSA) for mutant POT1 examining binding capacity to a telomere olignoculeotide. POT1^ΔOB refers to a protein deleted for the first DNA binding domain (aa127-635). (F) Immunoblot of in vitro translated products shows stable missense mutant POT1 at expressed levels, with the Myc immunoblot confirming specificity. (G) Mean intensity of binding relative to WT, with error bars representing SEM. The data shown are from 3 EMSA experiments derived from 2 independent in vitro translation reactions.