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Biology · Unit 6: Gene Expression and Regulation · 14 min read · Updated 2026-05-10

AP Biology Replication — AP Biology

AP Biology · Unit 6: Gene Expression and Regulation · 14 min read

1. Semiconservative Replication and Experimental Evidence ★★☆☆☆ ⏱ 4 min

Before the landmark Meselson-Stahl experiment, three competing models for DNA replication were proposed: conservative (parent helix remains intact, new daughter helix is entirely new), semiconservative (each daughter helix has one original parent strand and one new strand), and dispersive (parent strands fragment, each daughter has a mix of old and new).

Meselson and Stahl tested these models by growing *E. coli* in medium containing heavy nitrogen ($^{15}\text{N}$) to uniformly label all parental DNA, then transferred the bacteria to medium with only light nitrogen ($^{14}\text{N}$) and separated DNA by density after each replication generation. Their results ruled out conservative and dispersive models, confirming semiconservative replication as correct.

2. Replication Fork Mechanism and Enzyme Functions ★★★☆☆ ⏱ 4 min

The replication fork is the Y-shaped region where DNA is unwound and new strands are synthesized. A core constraint shapes all replication: all DNA polymerases can only add nucleotides to the free 3' hydroxyl end of a pre-existing strand, so all new strands are always synthesized 5' → 3'. Because the two parent strands are antiparallel, this produces two distinct types of new strands at the fork:

  • **Leading strand**: synthesized continuously toward the opening replication fork, since its 3' end points toward the fork.
  • **Lagging strand**: synthesized in short, discontinuous segments called Okazaki fragments, because its 5' end points toward the fork, so new 3' template ends are exposed as the fork opens.

Key enzymes act in sequence at the replication fork:

  1. Helicase: Unwinds the double helix and separates parent strands
  2. Single-strand binding proteins (SSBs): Keep separated strands from reannealing
  3. Topoisomerase: Relieves supercoiling ahead of the fork
  4. Primase: Synthesizes a short RNA primer to provide the 3' OH DNA polymerase needs to start
  5. DNA polymerase: Extends the new strand
  6. DNA ligase: Joins Okazaki fragments on the lagging strand after primer removal

3. Prokaryotic vs Eukaryotic Replication and Telomeres ★★★☆☆ ⏱ 3 min

Prokaryotes have a single circular chromosome, so replication starts at one origin of replication and proceeds bidirectionally around the circle until completion. Eukaryotes have long linear chromosomes, so they use multiple origins of replication along each chromosome to replicate the entire genome in a reasonable timeframe during S phase.

A key unique problem for eukaryotes is the end-replication problem: because RNA primers at the 5' end of the new strand cannot be replaced with DNA (there is no upstream 3' OH end to extend from), each round of replication shortens the chromosome by the length of the terminal primer. To protect coding DNA from being lost, eukaryotic chromosomes have non-coding repetitive sequences at their ends called telomeres. In germ cells, stem cells, and most cancer cells, the enzyme telomerase adds new telomere repeats to the ends of chromosomes, preventing shortening. Most somatic cells do not have active telomerase, so their chromosomes shorten with each division, a process linked to aging and cellular senescence.

4. AP Style Concept Check ★★☆☆☆ ⏱ 3 min

Common Pitfalls

Why: Students confuse the orientation of the parent template strand with the direction of synthesis of the new strand

Why: Students incorrectly expect the original heavy double helix to remain intact after the first generation

Why: Students mix up the functions of helicase and topoisomerase

Why: Students generalize telomerase function from germ cells to all cell types

Why: Students confuse DNA polymerase with RNA polymerase, which can start synthesis de novo

Quick Reference Cheatsheet

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