Before a cell divides, every DNA molecule in its nucleus is copied, accurately, during the S phase of interphase. Each strand serves as a template, so every new molecule keeps one parent strand: replication is semi-conservative.
DNA is copied during the S phase of the cell cycle. The hydrogen bonds between bases break and the double helix unwinds, so each strand is exposed as a template. Free DNA nucleotides pair with the exposed bases by complementary base pairing (A with T, C with G). DNA polymerase joins the new nucleotides by forming phosphodiester bonds, but it can add nucleotides only to the 3′ end of a growing strand, so new DNA is always built in the 5′ to 3′ direction. On one template the new strand grows towards the replication fork continuously (the leading strand); on the other it must grow away from the fork, in short fragments (the lagging strand), which DNA ligase joins with phosphodiester bonds. Each daughter molecule has one original and one new strand: replication is semi-conservative.
Fig. 1: a replication fork; new DNA grows only 5′ to 3′, so one new strand is continuous and the other is made in fragments
Section 01
A fork that copies both strands.
Press Replicate and follow the fork from left to right. The old strands are blue and the new strands orange; DNA polymerase is green and DNA ligase flashes pink each time a fragment is finished. Watch the LAGGING FRAGMENTS counter rise while the LEADING STRAND readout stays continuous.
When: in the S (synthesis) phase of interphase, so that each daughter cell receives an identical copy after mitosis.
Unzipping: the hydrogen bonds between complementary bases break and the two strands separate; both strands act as templates.
Free nucleotides: activated DNA nucleotides in the nucleus pair with the exposed bases: A with T, T with A, C with G, G with C.
DNA polymerase: moves along the template and joins each new nucleotide to the 3′ end of the growing strand by a phosphodiester bond (a condensation reaction). It reads the template 3′ to 5′ and builds the new strand 5′ to 3′.
DNA ligase: joins the short lagging-strand fragments together by forming phosphodiester bonds across the gaps, making one continuous strand.
Leading strand
Lagging strand
its template runs 3′ to 5′ towards the fork
its template runs 5′ to 3′ towards the fork
new strand grows in the same direction as the fork moves
new strand grows away from the fork
made continuously by DNA polymerase
made as short fragments, each started as the fork opens more template
no joining needed along its length
fragments joined by DNA ligase
Examiner trap
Do not say DNA polymerase builds the lagging strand 3′ to 5′. It never does: both new strands are made 5′ to 3′. The lagging strand is in fragments precisely because its 5′ to 3′ direction points away from the fork.
Stage 1 · Learn
Check what the sim just showed you
Four quick checks. Each correct answer earns XP and records this skill on your profile.
Quick check+10 XP
In the replication simulator, what colour are the newly made strands?
Quick check+10 XP
As the fork moves, the LAGGING FRAGMENTS counter keeps rising. Why are fragments needed on that strand?
Quick check+10 XP
What is happening when the pink DNA ligase flashes in the simulator?
Quick check+10 XP
When replication in the simulator is complete, how is each daughter molecule made up?
Section 02
Why semi-conservative?
Three models were once possible: conservative (the parent molecule stays whole), semi-conservative (each new molecule has one old strand) and dispersive (old and new DNA mixed in both strands). Density experiments with heavy nitrogen decided between them.
The experiment: bacteria were grown for many generations on 15N (heavy nitrogen), so all their DNA was heavy, then moved to 14N (light). DNA was extracted after each generation and spun in a density gradient by centrifugation.
After one generation: a single band of intermediate density. This rules out conservative replication, which would give one heavy and one light band.
After two generations: one intermediate band and one light band, in equal amounts. This rules out the dispersive model, which would give a single band moving gradually towards light.
Why it matters: keeping a complete original strand as the template, plus complementary base pairing, makes copying extremely accurate, so genetic information is passed on unchanged.
Generation in 14N
Heavy (15N/15N)
Intermediate (15N/14N)
Light (14N/14N)
0
100%
0%
0%
1
0%
100%
0%
2
0%
50%
50%
3
0%
25%
75%
Examiner trap
The intermediate band never disappears in later generations: the two original heavy strands are kept, so there are always exactly two hybrid molecules. Only their proportion halves each generation.
Stage 2 · Exam
Exam-style questions
Unlocks once the four checks above are done. Worth more XP, written to AS Paper 1 and Paper 2 standard.
Finish the four checks above to unlock the exam questions
Exam style+20 XP
During which stage of the cell cycle does DNA replication take place?
Exam style+20 XP
Bacteria with only 15N DNA are moved to a 14N medium and allowed to replicate twice. Which result supports semi-conservative replication?
Exam style+20 XP
Which statement about DNA polymerase is correct?
Exam style+20 XP
A template strand has the sequence 3′ TACGGA 5′. What is the new strand built on it?
Skill unlocked
Semi-conservative replication, mastered.
This skill is now recorded on your profile. Keep the chain going.