FIGURE 14.
Mechanism of RNA-DNA primer synthesis by the human primosome. At the first step (steps are labeled by roman numerals at the circle in the center), p58C moves toward p49 (curved arrow) to initiate RNA synthesis. During the second step, p58C is moving toward p180core by following the helical path of the growing DNA/RNA duplex (curved arrow) and pushes the p180core to dissociate from the platform (straight arrow). Additionally, when RNA primer length is nine nucleotides, p58C makes a steric hindrance with p58N, which prevents primer extension by p49. At the third step, p58C rotates (curved arrow) and loads the template/primer to the Polα active site. At the fourth step, Polα extends the RNA primer with dNTPs, whereas p58C is holding the 5′ terminus of the primer. At the fifth step, primosome is replaced by Polϵ or Polδ. Models of primosome at different steps of primer synthesis are based on the apo-primosome structure (Fig. 2) and primase models (Fig. 8).