Notes on Discontinuous Replication and Okazaki Fragments

Discontinuous replication

• DNA replication is discontinuous on the lagging strand and continuous on the leading strand.

Lagging strand and Okazaki fragments

• Okazaki fragments are short DNA segments synthesized on the lagging strand in the $5' \rightarrow 3'$ direction.

• Each fragment requires an RNA primer to initiate synthesis.

• Synthesis is in the opposite direction to the overall replication fork movement.

Sequence of events on the lagging strand

1. Primase lays down an RNA primer.

2. DNA polymerase extends the fragment from the primer ($5' \rightarrow 3'$) until it reaches the next primer.

3. RNA primers are removed and replaced with DNA by another DNA polymerase (e.g., DNA Pol I in bacteria).

4. DNA ligase seals the remaining nicks between fragments by forming a covalent phosphodiester bond, creating a continuous strand.

Key concepts

• DNA synthesis always proceeds in the $5' \rightarrow 3'$ direction.

• This mechanism is crucial for genome integrity and explains the need for telomere maintenance in eukaryotes.

Quick summary of enzymes

• Primase: Synthesizes RNA primers.

• DNA Polymerase: Extends DNA fragments and replaces RNA primers with DNA.

• DNA Ligase: Seals nicks to join Okazaki fragments, forming phosphodiester bonds, using ATP (eukaryotes) or NAD+ (bacteria) for energy.