BiologyIntermediate3D simulation~15 min

DNA Replication

Every time a cell divides, it must copy all of its DNA, accurately, in a matter of hours. Watch a replication fork in action: helicase unzips the helix, primase lays primers, DNA polymerase builds the new strands, and ligase stitches the fragments together.

Replicating Click a base or an enzyme
t = 0.0 s
1

How fast the fork moves. Real forks copy about 50 bases per second in human cells.

Key

  • Original (template) strand
  • New DNA strand
  • RNA primer
  • A (adenine)
  • T (thymine) / U (uracil in RNA)
  • G (guanine)
  • C (cytosine)
What is happening
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Fork position
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New bases added
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Okazaki fragments joined
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How to use this simulator

  1. Press Start and watch the fork move to the right as helicase unzips the helix.
  2. Follow the leading strand (bottom): it is built continuously, right behind the fork.
  3. Follow the lagging strand (top): primase lays a pink RNA primer, DNA polymerase builds a fragment backwards, then the primer is swapped for DNA and ligase seals the gap.
  4. Click any base to see its name, its partner and which strand it belongs to. Click an enzyme to learn its job.
  5. Slow it down with Speed to watch each step. Reset starts again with a new random sequence.

What DNA replication is

DNA replication is the process of copying a DNA molecule before a cell divides, so each new cell receives a complete set of genetic instructions. It happens during the S phase of the cell cycle. In human cells, about 6 billion base pairs are copied, starting at thousands of points called origins of replication so the job finishes in hours rather than weeks.

DNA structure in brief

DNA is a double helix: two strands, each a chain of nucleotides with a sugar-phosphate backbone and abase (A, T, G or C). The bases pair across the middle by hydrogen bonds: A with T andG with C. The strands are antiparallel: one runs 5′→3′ and its partner runs 3′→5′, which is why the labels at the ends of the strands in the simulator alternate.

Step by step

  1. Unwinding: helicase breaks the hydrogen bonds between bases, opening a Y-shaped replication fork.
  2. Priming: primase makes a short RNA primer (3 bases in the model; about 10 in real cells). DNA polymerase cannot start a strand from nothing.
  3. Elongation: DNA polymerase III adds nucleotides that pair with the template, always to the 3′ end of the growing strand.
  4. Primer removal: DNA polymerase I removes the RNA primers and fills the gaps with DNA.
  5. Joining: DNA ligase seals the remaining nicks in the backbone, producing continuous strands.

Other proteins help too: single-strand binding proteins stop the separated strands from re-pairing, and topoisomerase relieves the twisting that builds up ahead of the fork. They are left out of the model to keep it clear.

Leading and lagging strands

DNA polymerase can only build in the 5′→3′ direction. Because the two templates are antiparallel, on one of them that direction follows the fork: the leading strand is made continuously from a single primer. On the other, 5′→3′ points away from the fork, so the lagging strand is built in short pieces calledOkazaki fragments, each with its own primer. In bacteria they are 1,000–2,000 bases long; in eukaryotes, about 100–200.

Semi-conservative replication

When copying finishes, each new molecule has one original strand (blue in the simulator) and onenew strand (orange). This is called semi-conservative replication. Matthew Meselson and Franklin Stahl proved it in 1958 by growing bacteria in heavy nitrogen, moving them to normal nitrogen, and measuring the density of the DNA after each generation.

Speed and accuracy

Bacterial replication forks move at around 1,000 bases per second; human forks at about 50. DNA polymerase alsoproofreads: it can remove a wrongly paired base immediately. Together with later repair systems, the final error rate is roughly one mistake per billion bases copied. The rare errors that slip through aremutations, which are the raw material for natural selection.

Key terms

Template strand
An existing strand used as the pattern for building a new one.
Replication fork
The Y-shaped region where the helix is being unzipped and copied.
Okazaki fragment
A short stretch of new DNA on the lagging strand.
Primer
A short RNA strand that gives DNA polymerase a 3′ end to build onto.
5′ and 3′ ends
The two chemically different ends of a strand, named after carbon atoms in the sugar.

Common misconceptions

  • “The new DNA molecule is completely new.” Each daughter molecule keeps one original strand.
  • “The lagging strand is made more slowly or later.” Both strands are made at the same overall rate; the lagging one is just made in pieces.
  • “DNA polymerase can start a strand anywhere.” It needs a primer with a free 3′ end.

Key takeaways

  • Helicase unzips; primase primes; DNA polymerase builds; ligase joins.
  • Bases pair A–T and G–C, so each strand is a template for its partner.
  • Polymerase only works 5′→3′, giving a continuous leading strand and a fragmented lagging strand.
  • Replication is semi-conservative: each copy is half old, half new.

Model note: one fork copying 40 base pairs, greatly slowed down. The two primers left at the ends are removed by enzymes from the neighbouring fork in a real chromosome, and at chromosome tips by telomerase.

Knowledge check

DNA Replication: test your understanding

Answer each question to get instant feedback and an explanation. Use the simulator to check your thinking.

8 questions3 basic3 intermediate2 advanced

0 of 8 answered

  1. Q1BasicWhich enzyme unzips the DNA double helix at the replication fork?
    Show answer

    Answer: B. Helicase

    Helicase breaks the hydrogen bonds between base pairs, separating the two strands so each can act as a template.

  2. Q2BasicA template strand reads A T G C. What is the new complementary DNA strand?
    Show answer

    Answer: B. T A C G

    A pairs with T and G pairs with C, so A T G C is copied as T A C G. (U only appears in RNA, such as primers.)

  3. Q3BasicWhy is DNA replication called semi-conservative?
    Show answer

    Answer: B. Each new DNA molecule contains one original strand and one newly made strand

    Each parent strand serves as a template and stays paired with its new partner, so both daughter molecules are half old and half new.

  4. Q4IntermediateWhy is the lagging strand made in short Okazaki fragments?
    Show answer

    Answer: B. DNA polymerase can only add nucleotides in the 5′→3′ direction, which on this strand points away from the fork

    The two template strands are antiparallel. On one, 5′→3′ synthesis follows the fork (leading strand); on the other it runs away from it, so it must restart repeatedly.

  5. Q5IntermediateWhat is the job of primase?
    Show answer

    Answer: B. To lay a short RNA primer that gives DNA polymerase a starting point

    DNA polymerase can only extend an existing strand. Primase makes a short RNA primer that polymerase can build onto.

  6. Q6IntermediateAfter DNA polymerase I replaces an RNA primer with DNA, what is still needed?
    Show answer

    Answer: B. DNA ligase must seal the nick in the sugar-phosphate backbone

    A gap in the backbone (a nick) is left between the fragments. DNA ligase forms the final bond to join them into one continuous strand.

  7. Q7AdvancedIn the simulator, a new base on the lagging strand shows the letter U. What does that tell you?
    Show answer

    Answer: B. That base is part of an RNA primer, because RNA uses uracil instead of thymine

    Primers are RNA, and RNA uses uracil (U) to pair with adenine. Once DNA polymerase I replaces the primer, the U becomes T.

  8. Q8AdvancedIn the Meselson–Stahl experiment, bacteria grown in heavy nitrogen (¹⁵N) were moved to normal nitrogen (¹⁴N). After one round of replication, all DNA had an intermediate density. Which model did this support?
    Show answer

    Answer: B. Semi-conservative or dispersive replication; a second round ruled out dispersive

    One hybrid band ruled out the conservative model. After a second round, half the DNA was hybrid and half light, which only the semi-conservative model predicts.

References and further reading

  1. Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e, Section 14.4: DNA Replication in Prokaryotes. OpenStax. openstax.org (opens in a new tab)
  2. Clark, M. A., Douglas, M., & Choi, J. (2018). Biology 2e, Section 14.3: Basics of DNA Replication. OpenStax. openstax.org (opens in a new tab)
  3. Meselson, M., & Stahl, F. W. (1958). The replication of DNA in Escherichia coli. PNAS, 44(7), 671–682. doi.org (opens in a new tab)

This simulator is a simplified educational model. Found an error? Let us know. See our educational disclaimer.