🗻 Big Picture: DNA is a crucial molecule that carries the genetic information necessary for every organism and virus on earth to develop, grow, and function. In order to do its job, DNA must create a copy of itself to put in each of the two cells it creates when it divides, and it does so through a process called DNA replication.
You've probably heard of DNA as the genetic blueprint of our cells, but a better term might be the genetic template. Why? You create a blueprint from scratch to make something once, but you use a template over and over again to create identical copies of the same item. That's how DNA replication works, and it may seem intimidating, but it really isn’t as complicated as you might think. Let's get into it.
Deoxyribonucleic acid, or DNA, is the molecule that contains the unique genetic material of nearly every organism on earth. In other words, DNA is what makes you, “you”.
DNA was first identified in the 1860s by Swiss chemist Friedrich Miescher. However, it wasn’t until the 1950s that we knew what it actually looked like.
In 1953, James Watson and Francis Crick used images of DNA obtained by Rosalind Franklin to create their unique, double-helical model of DNA that resembles a twisted ladder.
DNA is made up of two long matching strands of nucleotide bases ─molecules that are essentially the building blocks of our genetic material.
There are four types of bases: adenine (A), thymine (T), guanine (G), and cytosine (C). The bases of each strand of DNA are bound together by hydrogen bonds to create the unique structure of the twisted double helix.
DNA replication is an important phase of the cell cycle ─an ordered series of events that take place as a cell grows and divides. It’s split into 4 phases: gap 1 (G1), synthesis (S), gap 2 (G2) and mitosis (M).
DNA replication occurs in the synthesis, or S phase, of the cell cycle. During this phase, the entire parent cell’s DNA is copied into two new strands that will be used to create a pair of identical daughter cells.
As discussed before, DNA’s unique double-helical shape was discovered by James Watson and Francis Crick in 1953. It wasn’t until four years later, however, that we gained a clear idea of how it actually replicates.
Before we discovered the actual series of steps of DNA replication, three hypotheses existed to explain how it might occur. These hypotheses were categorized as the conservative, semi-conservative, and dispersive models.
Today, we know conclusively that DNA replication follows the semi-conservative model, in which each strand of the original DNA’s double helix acts as a template for a new, complementary strand, as proven by the Meselson-Stahl Experiment in 1957.
Before a cell can divide, it needs to make two copies of its DNA to allocate into each of its new daughter cells. This process, called DNA replication, occurs in the S phase of the cell cycle in three stages: Initiation, Elongation, and Termination.
Seven important enzymes and proteins catalyze DNA replication: DNA helicase, the SSB protein, DNA tospieromase, DNA primase, DNA polymerase, DNA exonuclease, and DNA ligase. Here’s how the process is done.
(If you’re a visual learner, check out our interactive simulation at the top of the page to see what replication looks like and to go through the steps yourself!)
After the double-helix has been “unzipped”, the single stranded binding protein, or SSB protein, binds to the newly separated DNA strands to hold them in place. If the SSB protein is not present, the individual strands of DNA would bind back together and the process of replication could not occur.
As helicase further unwinds the DNA, the still zipped portion of the DNA behind the replication fork winds tighter and tighter. This is known as supercoiling.
If the coil gets too tight, it will physically prevent helicase from moving further down the strand. DNA topoisomerase relieves this strain so that the process of replication can continue.
With the SSB protein in place and supercoiling relieved, DNA primase creates a strand of RNA bases called a primer. Primers are bound to each unzipped half of the DNA, and serve as the starting point for the assembly of new DNA strands in the next step of replication, elongation.
Before you read this section, it is HIGHLY recommended that you complete the interactive simulation, as elongation is the most complex portion of the DNA replication process.
During elongation, the enzyme DNA polymerase binds to the primer and moves along each strand, adding complementary nucleotide bases to each half of the original DNA as visualized in the image above. (Remember─A always pairs with T, and C always pairs with G).
This process occurs continuously and in one direction on the upper, or leading strand of DNA.
For the lower, or lagging strand, however, this process is not continuous and has a slightly different process than that of the leading strand. Here’s the rundown for both.
Let’s start by taking a look at DNA as it replicates in the image below and establish a few basic facts:
Okay, now that we’ve got that down, let’s unpack the diagram.
The upper parental strand runs 5’ to 3’ from left to right. The leading strand is oriented inversely to its parent strand, running 5’ to 3’ from right to left toward the replication fork.
The lower parental strand runs 3’ to 5’ from left to right. Its complementary lagging strand runs 5’ to 3’ away from the replication fork.
We already know that DNA synthesis always moves toward the replication fork and that DNA polymerase can only synthesize DNA in the 5’ to 3’ direction. This makes things easy for the leading strand, as DNA polymerase can easily and continuously add nucleotides from 5’ to 3’ in the direction of the replication fork’s movement.
Because of its orientation, the leading strand only requires one primer from which to bind and attach nucleotides in DNA synthesis.
The lagging strand runs from 5’ to 3’ away from the replication fork. Because DNA synthesis always moves toward the replication fork, and DNA polymerase can only add nucleotides in the 5’ to 3’ direction, DNA cannot be synthesized continuously toward the fork in the lagging strand. Instead, it must be added in a series of chunks, known as Okazaki fragments.
Each Okazaki fragment requires its own individual RNA primer from which to attach its nucleotide bases. As DNA synthesis occurs, DNA primase attaches a new primer further up the lagging strand toward the replication fork.
DNA polymerase then attaches a new Okazaki fragment to this primer in the 5’ to 3’ direction, moving in the direction opposite to the replication fork. As the fork continues to open, a new primer is added further up the lagging strand, and a new Okazaki fragment is synthesized. This process is repeated until the new DNA has been completed.
Okay, so we finished making the DNA. We’re done now, right? Nope! After elongation comes the final stage of the DNA replication process: termination. During termination, the enzymes DNA exonuclease and DNA ligase serve as a cleanup crew for all of the other enzymes and proteins utilized during replication.
DNA exonuclase’s job is to remove all of the residual primers from both the leading and lagging strands of DNA. Once this is done, DNA polymerase makes another appearance, filling in all of the gaps with their appropriate base pairs.
Now it’s DNA ligase’s turn to seal together both strands, serving as the glue that binds each new strand of DNA together. Finally, the strands re-coil into their original twisted ladder shape, and the process of DNA replication is complete.
We should now have two new complete strands of DNA, both identical to the original strand. Each double-strand is formed with one old, conserved strand of DNA, and one newly synthesized one.
DNA is the carrier of genetic information.
DNA is a molecule composed of two identical strands of nucleotide bases.
Each original strand of DNA serves as a template from which to synthesize new strands.
DNA was first identified by Friedrich Miescher in the 1860s. James Watson and Francis Crick used images of DNA obtained by Rosalind Franklin to create their double-helical model in 1953.
DNA replication occurs during the S phase of the cell cycle.
DNA replication follows the semi-conservative model, because each new daughter strand contains both one one newly synthesized and one original, or conserved, strand of DNA.
DNA replication occurs over 3 stages: Initiation, Elongation, and Termination.
During initiation, DNA helicase uncoils and separates the two original strands of DNA. The SSB protein keeps these strands from binding together, and DNA topoisomerase keeps the DNA from supercoiling. DNA primase then creates primers which bind to each newly separated half of the original double-stranded DNA.
During elongation, DNA polymerase adds complementary nucleotide bases to each strand.
The leading strand of DNA produces DNA continuously, while the lagging strand must produce DNA in chunks called Okazaki fragments.
During termination, DNA exonuclease removes all residual RNA primers from the leading and lagging strands, which are replaced with the appropriate nucleotide bases by DNA polymerase. DNA ligase seals together each new strand of DNA.
You made it to the end! Congratulations, we’re so proud of you! 🎉 🧑🎓🎊 Hopefully you now know all about DNA replication–where it occurs, how it happens, and all of the important enzymes and proteins that play a part in the process. To check your understanding, take a look at some of common FAQs about DNA replication below.
1. What are the four nucleotide bases, and how do they pair together?
Adenine (A), thymine (T), guanine (G), and cytosine (C). A always pairs with T, and G always pairs with C.
2. In what phase of the cell cycle does DNA replication occur?
The S phase.
3. What model does DNA replication follow? What does it mean?
The semi-conservative model, in which each strand of the original DNA’s double helix serves as a template for a new, complementary strand.
4. What are the three stages of replication?
Initiation, elongation, and termination.
5. What enzyme relieves supercoiling?
6. What enzymes are involved in termination, and what do they do?
DNA exonuclease, DNA ligase, and DNA polymerase are all involved in termination. DNA exonuclease removes all residual primers from the leading and lagging strands of DNA, and DNA polymerase fills the gaps left behind. DNA ligase seals the new strands of DNA together.
7. Why can’t DNA polymerase synthesize DNA continuously on the lagging strand?
DNA polymerase can only add nucleotides from the 5’ to 3’ end of a strand of DNA, and DNA synthesis always moves toward the replication fork. The lagging strand runs 5’ to 3’ away from the replication fork, so new DNA must be added in chunks called Okazaki fragments.
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