Extended Data Fig. 5: RPA49 linker runs along the Pol I clamp to position the tWH domain.

a, Cartoon domain representation of the RPA49 subunit. The colored bar indicates the region modeled in the structure denoted as ‘built’. DM – dimerization domain; HTH – helix-turn-helix motif; WH – winged helix domain. b, Overall arrangement of the RPA49 subunit (purple, cartoon representation fitted into the cryo-EM density extracted from Map C) on the surface of Pol I (grey, surface representation). The DNA scaffold is shown as a cartoon. c, Positioning of the tWH domain (purple, cartoon representation fitted into the corresponding cryo-EM density) near the RNA exit tunnel. The Pol I core is shown in a surface representation colored by subunit. Right panel: yeast tWH domain (pink, cartoon representation) from PDB: 5M64³⁰ overlaid onto the human Pol I structure. d, Left panel: the linker (purple) wraps around a knob formed by clamp coiled-coils (grey, surface representation). Middle panel: partially disordered loop (gold highlight) connecting the coiled-coils (grey cartoon representation) allows binding of the RPA49 linker (purple cartoon). Right panel: in the structure of human Pol I bound to RRN3, where the RPA49 linker is disordered, the same loop (golden highlight) adopts a conformation that would clash with the RPA49 linker. e, HTH motif within the linker (purple with the corresponding cryo-EM density shown in transparent representation) is positioned close to the downstream DNA helix (blue, cartoon representation). Right panel: side chains of the HTH are shown in stick representation (purple). Helix 1 and turn contact the RPA2 lobe (wheat outline), while helix 2 can contact the downstream DNA. f, Sequence alignment of the part of RPA49 linker containing the HTH motif between human and yeast. Dark blue marks identical residues and light blue similar residues. Dots mark gaps in the sequence.