Fig. 6: Disease-associated mutations of Pol I.

a, Overview of the mutations affecting Pol I. The structure is shown in cartoon representation (gray), with nucleic acids marked in blue (DNA) and red (RNA). Disease-causing mutations for TCS (green) and AD (magenta) are shown in sphere representation. b–g, Close-up views of the residues affected by the mutations (stick representation). Other Pol I residues that can make contacts with the mutated one are also shown in stick representation. Putative hydrogen bonds are shown with black, dashed lines. b, S682 residue from RPA1. c, R1003 residue from RPA2. d, E593 residue from RPA1. Active-site residues found in close proximity to the E593 residue are shown in stick representation. e, V1299 residue from RPA1. f, Cluster of mutations in the RPAC2 subunit. Only residues affected by mutations and those that can form hydrogen bonds with them are shown for simplicity. g, RPAC1 residue R279 is shown in human Pol I (left panel) and in human Pol III (PDB: 7AE1 (ref. ³³)) (right). h, Cryo-EM density corresponding to the core (gray) of the human Pol I (left) and human Pol III (right). Subunit RPAC1 is shown in red, RPAC2 in orange, and Pol I-specific RPA34 in blue. N-terminal residues are shown in cartoon representation together with their corresponding density in gray (transparent representation). The first visible residue in Pol I (D38) is shown in stick representation. Residues mutated in HLD found in the RPAC1 N-terminus (visible in Pol III) are shown in stick representation (cyan) (right).