lagging strand

Meaning: DNA polymerase adds nucleotides only to a free 3′ OH, so every new strand grows 5′→3′. The two template strands are antiparallel. At the replication fork, the leading strand is made continuously toward the fork. The lagging strand is made in the direction away from the fork, so synthesis must restart each time helicase opens more template. This gives short Okazaki fragments. Primase lays down an RNA primer for each fragment, and DNA polymerase extends it. The primers are then removed and replaced with DNA (DNA polymerase I in prokaryotes), and DNA ligase seals the nicks between fragments.

On the MCAT: A passage shows a fork diagram and asks which strand is continuous, which has Okazaki fragments, or which needs many primers. The leading strand needs one primer per fork, and the lagging strand needs one per fragment. A common question gives a mutant, such as a ligase-deficient cell, and asks you to predict the result: short unjoined fragments build up on the lagging strand. Okazaki fragments are longer in prokaryotes than in eukaryotes.

Common confusion: Students think the lagging strand is made 3′→5′, or that polymerase runs backward. Polymerase always extends 5′→3′ on both strands. The lagging strand is made in pieces because its direction of synthesis is opposite to the direction the fork opens.