How does DNA replication work?
DNA replication unwinds the double helix and uses each strand as a template for a new one, so every new molecule keeps one old strand and gains one new strand (semiconservative replication). DNA polymerase can only add nucleotides to a 3' end, which is why one strand is copied continuously and the other in pieces.
Watch it explained
How does DNA copy itself?
A recording of a 3D scene of DNA replication: the double helix, its 5′ and 3′ ends marked, turns as helicase and topoisomerase arrive at the replication fork and the parent strands are pulled apart, then primase lands on each separated strand.
Labeled in the scene:
- Parent strand
- Helicase
- Topoisomerase
- Primase
The enzymes at the fork
Replication starts at origins of replication (one in a bacterial chromosome, many along each eukaryotic chromosome) and moves outward as two replication forks.
- Helicase unwinds the helix by breaking the hydrogen bonds between base pairs.
- Single-strand binding proteins keep the separated strands from snapping back together.
- Topoisomerase, working ahead of the fork, relieves the twisting strain that unwinding creates.
- Primase lays down a short RNA primer, because DNA polymerase cannot start a strand from nothing.
- DNA polymerase adds nucleotides to the primer's 3' end, matching A with T and G with C, and proofreads as it goes.
- The RNA primers are later replaced with DNA, and DNA ligase seals the gaps in the sugar-phosphate backbone.
Leading and lagging strands
The two strands of DNA run in opposite directions (antiparallel), and new DNA is always built 5' to 3'. On the leading strand, that direction matches the way the fork opens, so polymerase follows the fork continuously after one primer. On the lagging strand, polymerase has to work away from the fork, so the strand is made in short Okazaki fragments, each with its own primer, which ligase then joins.
In bacteria, the textbook names are DNA polymerase III for the main synthesis and DNA polymerase I for replacing primers; eukaryotes use different polymerases for the same jobs.
Common mistakes
- Saying polymerase builds 3' to 5'. It reads the template 3' to 5' and builds the new strand 5' to 3'.
- Saying primase makes a DNA primer. The primer is RNA.
- Giving ligase's job to helicase, or the other way round. Helicase separates strands; ligase joins fragments.
- Forgetting why replication is semiconservative: each daughter helix keeps one parent strand.
Replication happens in the S phase, before a cell divides; see meiosis vs mitosis for what comes next, and how a gene becomes a protein for how the same code is read.
Turn the fork around
The clip on this page is a recording of an Isotoon 3D model: the helix turns as helicase and topoisomerase arrive at the fork, the parent strands are pulled apart, and primase lands on each strand. On Pro, you can open a model like it yourself, turn it and step through each enzyme with a note at every step. Ask "How does DNA copy itself?" to start. More on the biology and AP Biology pages.
Questions
- How did scientists show replication is semiconservative?
- Meselson and Stahl grew bacteria on heavy nitrogen, moved them to light nitrogen, and separated the DNA by density. After one generation all DNA was of intermediate density, which fits one old strand plus one new strand.
- Why do chromosome ends get shorter?
- On the lagging strand, the last RNA primer at a linear chromosome's end cannot be replaced with DNA, so a little sequence can be lost each round. Telomeres are repeating ends that absorb that loss, and telomerase can extend them in some cells.