Impact of rare familial mutations on POT1 protein. (A) Schematic showing the position of germ line POT1 mutations identified in CLL families relative to OB domains (red) and ACD binding region (blue). Also shown are somatic POT1 mutations identified in previous studies of CLL patients^37,38  (unshaded background) and germ line mutations found in familial cutaneous melanoma^39,40  (peach background). (B) Cross-species conservation of POT1 amino acids subject to missense mutation in CLL families. (C) Schematic of the crystal structure of human POT1 N-terminal OB domains bound to a telomeric DNA sequence (PDB 3KJP), illustrating the proximity of tyrosine 36 to the DNA strand. OB domains are shown in gray, DNA in blue, and Tyr.36 is highlighted in magenta.