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DNA Replication Fork Explorer

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About This MicroSim

This interactive diagram shows the complete enzymatic machinery at a DNA replication fork. Students can explore 13 labeled structures including helicase, DNA Polymerase III, primase, Okazaki fragments, DNA Polymerase I, and DNA ligase. Each callout provides a detailed description and an AP Exam Tip highlighting common misconceptions and exam strategies.

How to Use

  • Explore Mode: Hover over any numbered marker or label to see a description of the structure, its function, and an AP exam tip.
  • Quiz Mode: Click the Quiz button to test your knowledge. Marker labels are hidden — click the correct marker when prompted to identify each structure. A gold star appears for each correct answer, and a celebration animation plays when you complete the quiz.

Structures at the Replication Fork

Parental DNA Double Helix

The original double-stranded DNA that serves as the template for replication. Each strand is used as a template to synthesize a new complementary strand (semiconservative replication).

Topoisomerase

Relieves torsional strain ahead of the replication fork by cutting, swiveling, and resealing DNA strands. Prevents supercoiling that would stall the fork.

Helicase

A ring-shaped enzyme that uses ATP energy to break hydrogen bonds between base pairs, unwinding the double helix at the fork junction.

Single-Strand Binding Proteins (SSB)

Coat exposed single-stranded DNA to prevent re-annealing and protect the template from nuclease degradation.

RNA Primer

A short RNA sequence synthesized by primase that provides the free 3'-OH group needed by DNA Polymerase III to begin synthesis. The leading strand requires only one primer; the lagging strand requires many.

DNA Polymerase III

The primary replication enzyme that synthesizes new DNA in the 5'→3' direction. It has proofreading ability (3'→5' exonuclease activity) with an error rate of about 1 in 10 billion base pairs.

Leading Strand

Synthesized continuously in the 5'→3' direction, following the movement of the replication fork. Requires only a single RNA primer.

Lagging Strand and Okazaki Fragments

Synthesized discontinuously as short fragments (Okazaki fragments), each 1,000–2,000 nucleotides long in prokaryotes. Each fragment requires its own RNA primer and is synthesized away from the fork.

Primase

An RNA polymerase that synthesizes RNA primers on the lagging strand template. Unlike DNA polymerase, primase can start new strands from scratch.

DNA Polymerase I

Removes RNA primers using 5'→3' exonuclease activity and replaces them with DNA nucleotides.

DNA Ligase

Seals the nicks between adjacent Okazaki fragments by forming phosphodiester bonds, creating a continuous sugar-phosphate backbone on the lagging strand.

Lesson Plan

Grade Level

9-12 (AP Biology)

Duration

10-15 minutes

Prerequisites

  • DNA structure (double helix, base pairing, antiparallel strands)
  • Enzyme function and specificity
  • 5'→3' directionality of nucleic acids

Activities

  1. Exploration (5 min): Use Explore mode to examine each enzyme at the replication fork. Pay attention to the difference between leading and lagging strand synthesis.
  2. Guided Practice (5 min): Discuss with a partner why the lagging strand must be synthesized in fragments. Trace the 5'→3' direction on both strands.
  3. Assessment (5 min): Switch to Quiz mode and identify all 13 structures. Aim for a perfect score.

Assessment

  • Identify all enzymes at the replication fork and state their functions
  • Explain why leading strand synthesis is continuous while lagging strand synthesis is discontinuous
  • Describe the roles of DNA Pol I and DNA Ligase in processing Okazaki fragments