Which polymerase synthesizes the leading strand in eukaryotes?

• A. DNA polymerase gamma
• B. DNA polymerase delta
• C. DNA polymerase alpha-primase
• D. DNA polymerase epsilon synthesizes the leading strand.

Answer: (D)

The enzyme best suited for leading-strand synthesis in eukaryotes is DNA polymerase epsilon. In replication, the leading strand is synthesized continuously in the 5' to 3' direction as the fork opens, and polymerase epsilon is the highly processive enzyme that performs this continuous elongation, aided by the PCNA sliding clamp and other replication factors. It also carries 3' to 5' exonuclease proofreading to maintain fidelity. The other enzymes have different roles: polymerase delta handles the lagging strand, making Okazaki fragments; polymerase alpha-primase starts synthesis by laying down an RNA primer and a short DNA segment but does not sustain long, continuous elongation; polymerase gamma is dedicated to replicating mitochondrial DNA, not the nuclear genome.