Biochemistry · Molecular Biology (DNA Replication, Repair, Transcription, Translation)

During eukaryotic DNA replication, the replication fork moves 5'→3' on both strands, yet DNA polymerase can only synthesize in the 5'→3' direction. Which of the following correctly describes the molecular resolution of this apparent paradox on the lagging strand?

  • A A special reverse DNA polymerase synthesises lagging strand DNA 3'→5' continuously
  • B Primase lays short RNA primers repeatedly; DNA pol synthesises Okazaki fragments 5'→3' away from the fork; they are later joined by ligase after primer removal and gap-filling by DNA pol I
  • C The lagging strand is synthesised as a continuous strand by a helicase-tethered polymerase that unwinds ahead
  • D Topoisomerase II synthesises short segments 3'→5' on the lagging strand template
Correct answer: B. Primase lays short RNA primers repeatedly; DNA pol synthesises Okazaki fragments 5'→3' away from the fork; they are later joined by ligase after primer removal and gap-filling by DNA pol I

Explanation

On the lagging strand template, discontinuous synthesis occurs: primase (DnaG in prokaryotes) places a short RNA primer every 100–200 nt; DNA polymerase III extends each primer 5'→3' away from the replication fork, creating Okazaki fragments. DNA polymerase I (prokaryotes) or RNase H/FEN1 + DNA pol δ (eukaryotes) removes primers and fills gaps. DNA ligase seals the nicks. This semidiscontinuous mechanism allows both strands to be replicated in the net direction of fork movement without any 3'→5' synthesis.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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