DNA replication: the fork, leading and lagging strands

Replication starts at a special place, the origin (called oriC in E. coli), where initiator proteins open the DNA. Two replication forks then move away in opposite directions: replication is bidirectional.

Polymerase III adds each new nucleotide to the 3'-OH end of the growing strand. The incoming nucleotide (a dNTP) gives up two of its phosphates (as pyrophosphate), which supplies the energy.

Because polymerase can only work 5' → 3', the two strands are copied differently:

• On one template, the new strand can be made continuously, in the same direction the fork moves, from a single primer: the leading strand.
• On the other template, it must be made away from the fork, in short pieces, each with its own primer: the Okazaki fragments (about 1,000-2,000 nucleotides). This is the lagging strand. Polymerase I replaces the RNA primers with DNA, and DNA ligase joins the pieces.

Since one strand is continuous and the other in pieces, replication is semi-discontinuous.

In bacteria, the two forks meet at a terminus, roughly opposite the origin, where a termination protein stops the helicase. Eukaryotic chromosomes are long and linear, so they have many origins, each with two forks, and several kinds of DNA polymerase, so the copying finishes in time.