DNA polymerases display an intrinsic 5'-3' polarity, so only one continuous new strand can be synthesized at the 3' end of the leading strand, which reads 5'-3'. Because the lagging strand is the antiparallel complement of the leading strand, its replication utilizes a series of Okazaki fragments.
1. Initiation of lagging-strand replication takes place at the primase-created replication fork of an RNA primer (short complementary RNA strand). Primase is a dnaG-coded RNA polymerase that binds to the DNA helicase, forming a primosome complex. Such priming of initiation is necessary because no known DNA polymerases are able to initiate replication.
2. Extension of Okazaki fragments is performed by DNA polymerase III.
3. RNA primers are removed by nucleolytic enzymes such as ribonuclease H (RNAse H), flap endonucleases (FENs)and Dna2 helicase/nucleases.
4. Okazaki fragments are linked by DNA ligase I, which forms phosphodiester bonds to generated a continuous DNA chain that is complementary to the leading strand.