Fig. 3: The initiation and elongation pathways of DNA synthesis.

Time-resolved images capture the precise order of intermediates in the initiation and elongation cycles of DNA synthesis. The structures imply that translocation follows a push-pull mechanism where the O-O1 loop of the finger subdomain acts as a pawl to facilitate unidirectional movement of the template through the gated actions of conserved tyrosine residues 714 and 719. The individual steps include: (1) movement of the DNA duplex, (2) opening of the O-O1 loop to form a hydrophobic pocket, (3) closing of the O-O1 loop, (4) first chemical bond formation, (5) reopening of the O-O1 loop, (6) reclosing of the O-O1 loop, and (7) second chemical bond formation with loop reopening. Color scheme: 5’ templating base (red for initiation and cyan for elongation), active site region (gray), Y714 and Y719 (purple), 3’ nucleotide on the primer (orange for initiation and green for elongation), dATP (blue), and dCTP (green). Abbreviations: O (O helix), O1 (O1 helix), and Y (tyrosine).