Genetic analysis identified Apollo variants in the patients. (A) Pedigrees and Apollo variants identified in individuals P1, P2 and P3 by Sanger sequencing. (B) Domain architecture of the human Apollo with the localization of the identified variants of P1, P2 and P3. NLS: nuclear localization signal; TBM: TRFH binding motif. (C) Ribbon representation of the 3D structure of human Apollo catalytic domain (pdb 5AHO,³⁹ with 2 coordinated zinc ions and 2 tartrate molecules at the active site. Details of the region surrounding L142 are given in the box at left, highlighting the hydrophobic core in which L142 participates, in the vicinity of motif A D145 (bond with motif B H247, itself bound to a tartrate molecule, which may represent the phosphodiester cleaved by the nuclease³⁹). (D) Co-immunoprecipitation of endogenous TRF2 with WT or mutated forms of FLAG-Apollo. Picture representative of 3 independent experiments.