The steps and the enzymes

Replication needs the coordinated action of many enzymes and proteins.

1. Unwinding the double helix.
2. Helicase moves along the helix and breaks the hydrogen bonds between paired bases, separating the strands. The Y-shaped region where the strands separate is the replication fork. It exposes the bases so they can pair with new nucleotides.
3. DNA polymerase builds the new strand. It adds nucleotides one at a time to the 3′ end of the growing strand; each incoming nucleotide must pair with the exposed base on the template strand.
4. Primase makes short pieces of RNA, called primers, that pair with the template. DNA polymerase cannot start a strand alone; it can only extend an existing 3′ end, so it needs the primer.
5. Leading and lagging strands. DNA polymerase works only in one direction: it reads the template from 3′ to 5′ and builds the new strand from 5′ to 3′. The two template strands are antiparallel, so:
   • On the template that runs 3′→5′ in the direction of the fork's movement, the polymerase follows the helicase continuously and makes a continuous new strand in the 5′→3′ direction: the leading strand.
   • On the other template (5′→3′), the polymerase cannot move continuously in the direction of the fork. The new strand is therefore made in short pieces called Okazaki fragments, each made 5′→3′ (away from the fork), each needing its own primer. This is the lagging strand.
6. Joining the fragments. After replication of a fragment, the RNA primers are removed and a type of DNA polymerase fills the gaps with DNA nucleotides. DNA ligase then joins the Okazaki fragments into a continuous strand.