10 September 2026 · 7 min read
DNA replication explained: the semi-conservative model and Meselson–Stahl
Helicase, polymerase, antiparallel strands and the density-gradient experiment that proved it — the full story in exam-ready order.
What 'semi-conservative' means
When a DNA molecule replicates, each of the two new molecules contains one original (parental) strand and one newly synthesised strand. Half of each molecule is conserved — hence semi-conservative. This matters because it keeps the base sequence identical between generations of cells, with the original strand acting as a template.
The steps in order
- DNA helicase breaks the hydrogen bonds between complementary bases, unwinding the double helix into two single strands.
- Each exposed strand acts as a template. Free DNA nucleotides are attracted to their complementary bases (A–T, C–G) and pair by hydrogen bonding.
- DNA polymerase joins adjacent nucleotides by condensation reactions, forming phosphodiester bonds in the sugar-phosphate backbone.
- Because the strands are antiparallel and DNA polymerase's active site is complementary only to the 3' end of the growing strand, new nucleotides are added in the 5' to 3' direction — so the two new strands are built in opposite directions.
The Meselson–Stahl experiment
Bacteria were grown for many generations in a medium containing heavy nitrogen (15N), so all their DNA was heavy. They were then transferred to light nitrogen (14N) and allowed to divide. DNA was extracted and spun in a centrifuge so it settled according to density.
After one generation all the DNA formed a single intermediate band — ruling out conservative replication, which would give one heavy and one light band. After two generations there were two bands: intermediate and light, in equal amounts. That is exactly what semi-conservative replication predicts.
Common exam traps
- Saying helicase 'breaks bonds between nucleotides' — it breaks hydrogen bonds between bases on opposite strands.
- Saying DNA polymerase forms hydrogen bonds — base pairing is spontaneous; the enzyme forms phosphodiester bonds.
- Forgetting to explain the 5'→3' direction in terms of enzyme–substrate complementarity when asked 'why'.
- Predicting generation 3 incorrectly: expect 1 intermediate : 3 light.
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Revise this properly
This guide covers part of Topic 1: Biological molecules. Inside A-Plus Biology you get 95 flashcards and 22 exam-style questions with mark schemes for this topic alone.