GeneticsStep-through18 minLesson 2 of 2

DNA Replication

Before a cell divides, it copies all of its DNA — about 6 billion base pairs in a human cell, in a matter of hours. Open a replication fork and follow the team of enzymes that unzips, primes, builds, and seals two perfect copies.
Parent DNA — two antiparallel strands3′5′5′3′original strandnew DNARNA primer
drag to open the fork

← drag right to replicate →

Parent
Result

Click a stage tab, drag the diagram, or use the ← → keys

Stage 1 of 7

Parent DNA

Two antiparallel template strands

Replication starts from a double-stranded parent molecule. Its two strands run in opposite directions — the top strand 3′ → 5′ and the bottom 5′ → 3′ as drawn. Each strand will serve as a template for a brand-new partner, following the base-pairing rules A–T and G–C.

  • Replication begins at origins of replication — many along each eukaryotic chromosome
  • Each origin opens into a bubble with a replication fork at each end
  • Both parent strands act as templates
  • Direction matters: new DNA can only be built 5′ → 3′
Predict before you continue

To copy DNA, the two strands have to come apart first. Which bonds get broken to unzip them?

Meet the enzymes

Tap one to see it at work in the fork.

Three things to keep straight

  • Only 5′ → 3′

    DNA polymerase can only add nucleotides to a 3′ end. Every other rule of replication — primers, leading vs. lagging strands, Okazaki fragments — follows from this one constraint.

  • Antiparallel templates

    Because the two template strands run in opposite directions, one new strand can follow the fork continuously while the other has to be built backward in short pieces.

  • Half old, half new

    Each daughter molecule keeps one parent strand. That's semiconservative replication — and it's why each strand can serve as a check on the other.

Leading vs. lagging strand

Leading strandLagging strand
Direction built5′ → 3′, toward the fork5′ → 3′, away from the fork
SynthesisContinuousDiscontinuous (Okazaki fragments)
RNA primersOneOne per fragment
Ligase neededRarelyTo join every fragment
How we know

How do we know replication is semiconservative?

In 1958, Matthew Meselson and Franklin Stahl grew bacteria on heavy nitrogen (¹⁵N), then moved them to light nitrogen (¹⁴N). After one generation, all the DNA had an intermediate density — ruling out the conservative model. After two generations, half was intermediate and half was light — ruling out the dispersive model. Only semiconservative replication fit both results.

Quick recap

  1. 1

    Unzip — Helicase breaks H-bonds at the fork; topoisomerase relieves strain ahead; SSBs keep strands apart.

  2. 2

    Prime — Primase builds short RNA primers to give DNA polymerase a free 3′ end.

  3. 3

    Build — DNA polymerase III adds nucleotides 5′ → 3′ — continuously on the leading strand, in Okazaki fragments on the lagging strand.

  4. 4

    Clean up — DNA polymerase I replaces RNA primers with DNA; DNA ligase seals the nicks.

  5. 5

    Result — Two identical DNA molecules, each with one original and one new strand.