DNA Structure & Replication

Recall that a nucleotide is a monomer of one of the 4 macromolecules. A chain (or polymer) of nucleotides forms a nucleic acid. There are two nucleic acids: DNA and RNA. Shown here is a general template of a nucleotide.

Before we get to those, however, let's review the structure of these monomers.

Every nucleotide consists of a sugar (shown as a blue pentagon), a phosphate group (shown as an orange circle), and a nitrogenous base (shown as a green rectangle. The sugar and phosphate group will be the same amongst all nucleotides within a nucleic acid.

The nitrogenous base is where the interesting bit is found, and this is the bit that determines what nucleotide the structure has formed. There are 4 possible nucleotides in DNA. The chemical structure of one - adenine - is shown here.

You do not need to memorize the chemical formula or structure of adenine - you simply must know the general structure shown above.

B. The 4 Nucleotides of DNA - ATCG

There are four possible nucleotides that are found through DNA. These are:

adenine (A)
thymine (T)
cytosine (C)
guanine (G)

Again, all that differentiates these 4 nucleotides is the nitrogenous base. The rest is identical as you can see in the shown polymer.

Please note that, which all 4 nucleotides are shown bonded in sequence here, that does not mean that a single strand MUST contain each nucleotide. You could technically have a nucleic acid consisting of nothing except adenines bonded to one another in a long line.

C. The 4 Nucleotides of RNA - AUCG

RNA is a little different from DNA, as we will discuss more later. However, for now, I just want to highlight the differences between their nucleotides. For one, the sugar present in these nucleotides is different. More importantly for us, however, thymine cannot be found in RNA. Instead, RNA contains the nucleotide uracil. Their chemical differences are shown here, but you need not memorize them.

DNA's Structure: The Double Helix

A Touch of History - Credit Where It's Due

There isn't much more famous nowadays in biology than the famous double helix - the shape of DNA. Obviously that wasn't always the case. In fact, DNA's structure wasn't accurately described until 1953 by James Watson and Francis Crick, although they were only able to do so because of a famous X-ray crystallography photograph taken by the talented and unfortunately often-overlooked chemist Rosalind Franklin, pictured here alongside her famous photograph 51. In fact, Francis and Crick were shown this photograph without permission by Rosalind, leading to a strife between the scientists.

We could spend months discussing the discovery of DNA's structure, but that is beyond the scope of the AP exam. As a result, let's focus on the biology less so than the history moving forward.

The Structure of DNA

DNA, or deoxyribonucleic acid, is the nucleic acid known for coding for all living things. Everything that makes you you is coded for in your DNA. The structure of the DNA is the double helix, sometimes referred to as a twisted ladder. However, there are some intricacies to this shape that you must be familiar with for the course.

Firstly, note that DNA consists of two strands. These strands (each a polymer of nucleotides) are connected to each other in the middle via hydrogen bonds, but more on that in a moment. These strands are antiparallel, meaning that they are parallel, but point in opposite directions. If they did not face opposite directions, there would be no way for the 'insides' of the strands to interact. Each strand has a 5' and a 3' end. So the 5' end of one strand is next to the 3' end of the other strand.

The outside of the strands are referred to as the sugar-phosphate backbone, so named because it is made up of sugars and phosphates. We will see those again when we revisit nucleotides.

The insides of the strand, shown here as simplified bars that connect to one another, are the nitrogenous bases (aka the nitrogen-containing bases). These are where the nucleotides gain their identities. Depending on the nitrogenous base, nucleotides in DNA are one of the following:

Adenine
Thymine
Cytosine
Guanine

When the nitrogenous bases connect via hydrogen bonds, they form a base pair. Adenine (A) pairs with thymine (T) and cytosine (C) pairs with guanine (G). These hydrogen bonds between these base pairs hold the two strands of DNA together. Without those hydrogen bonds, our DNA strands would separate and float around. However, this means that each strand must be complementary to the other. That is, strand 1 must have a T where strand 2 has an A. We will discuss that more when we get to DNA sequences.

DNA vs. RNA

Before we review move on to DNA sequences and DNA replication, I wanted to highlight the key differences between DNA and RNA, the two nucleic acids. First, please note that DNA is double-stranded whereas RNA is single-stranded. The sugar-phosphate backbones contain different sugars (RNA has ribose and DNA has deoxyribose) but are otherwise quite similar. There is one slight difference in the nitrogenous bases within these two nucleic acids as well. DNA has the nucleotide thymine (T) whereas RNA has uracil (U). The other 3 nucleotides (A, C, and G) are common to both DNA and RNA, however.

It's All About the Sequence

While it is important for us to be familiar with DNA's structure in this class, we are more concerned with DNA's function. When we start looking at the function of DNA in the next chapter, you will find that most of DNA's structure is largely ignored. The only thing we will focus on moving forward is the sequence, or order, of the nucleotides in DNA. An example DNA sequence could be 5'-ATTTGCACCGT-3'. That sequence can be VERY different from the sequence 5'-ATTAGCACCGT-3'. The difference between an A and a T may seem minute, but it can have drastic consequences on an organism as we will see when we move on to gene expression.

How Much DNA Do You Have?

"Human DNA is composed of a chain of roughly 32 billion bases. That strand is broken up into chromosomes, wrapped, and coiled to sit inside the nucleus of each cell. Our DNA is packed so tightly that if unwound, connected, and stretched out, each strand would be about six feet long. Each of our trillions of cells contains a tightly wound six-foot-long molecule coiled to one-tenth the size of the smalled grain of sand. If you uncoiled the DNA from each of the four trillion cells in your own body and put them end to end, your personal DNA strand would run almost to Pluto." (Some Assembly Required: Decoding Four Billion Years of Life, from Ancient Fossils to DNA by Neil Shubin).

DNA Replication - How We Got All That DNA

Why and When Replication Must Occur

DNA replication is the process by which a cell copies (replicates) its DNA. It's as simple as that - all in the name. However, it is important to remember when a cell does this and why it is a necessary step. First, recall that DNA is copied in the S phase of interphase, so before cell division occurs. Secondly, recall that DNA must be copied in preparation for cell division. If a cell is going to undergo mitosis or meiosis, it must copy its DNA via DNA replication to ensure that all daughter cells have the proper amount of DNA.

Overview of DNA Replication

DNA replication occurs in three main stages and involves many enzymes. The three stages and the primary enzymes found within them are:

Step 1: Unwinding

DNA helicase - unzips the DNA
Topoisomerase - begins unwinding and stabilizes the DNA molecule while it is being unwound
RNA primase - synthesizes an RNA primer that allows DNA polymerase to bind

Step 2: Synthesis

DNA polymerase - synthesizes the new DNA strand using the template strand

Step 3: Ligation

DNA ligase - 'staples' the fragments of DNA together to form a cohesive strand

We will go more in-depth into these three steps and these enzymes, but this list is a simplified form of what you should know from each step, so it is a good introduction and review tool.

Step 1 - Unwinding

Topoisomerase begins unwinding DNA
DNA helicase unzips the DNA, forming the replication fork by breaking the hydrogen bonds between the two strands.

Shown here is the replication fork - so called because it looks like a fork in the road - formed by separating the two DNA strands.

Now that the nucleotides are exposed, new base pairs can be added into the inside to start forming new strands.

With the bases exposed, now RNA primase will add short pieces of RNA called primers to each strand.

These primers are going to be where a new DNA strand will start forming! Without a primer, step 2 (synthesis) of DNA replication cannot occur.

Shown in this image is just one primer being added to one strand. Then, DNA is added afterward by DNA polymerase. We will see a more detailed representation of the process in step 2.

Step 2 - Synthesis

Now that RNA primase has added a primer to the DNA template strands, DNA polymerase can bind and start synthesizing new strands using complementary base pairing (A-T, C-G).

As amazing as DNA polymerase is, it is actually quite limited! It can only synthesize DNA in the 5'-->3' direction. This is referring to the direction of the strand it is synthesizing, not the template strand. Due to this limitation, the two strands are not created equally. One strand will be easy to synthesize and the other far more difficult.

As you can see here, there is a leading strand shown on top. This strand it much easier for DNA polymerase to synthesize because it can follow DNA helicase into the replication fork and just keep following along and adding to its new strand. This is sometimes called continuous synthesis.

The other strand, known as the lagging strand, is so called because it is more difficult and slower to synthesize. But let's investigate why.

Remember that DNA is continually unzipping from right to left in this image.

As mentioned, DNA polymerase can only synthesize in the 5' --> 3' direction. So, it will basically be playing catch-up on the lagging strand. Instead of one fluid motion following along the path of DNA's unzipping, it will constantly be going in the direction opposite the replication fork. This means that it will require many RNA primers and form many Okazaki fragments, little pieces of DNA that are formed along the lagging strand. Because this synthesis is occurring in bits and pieces, it is considered discontinuous DNA synthesis.

The last part of step 2 is the removal of those pesky RNA primers. We can't have all these bits of RNA mixed in with our DNA! So, DNA polymerase goes back and replaces those RNA primers with short DNA strands.

Step 3 - Ligation

Finally, DNA ligase, another enzyme, comes in and staples the gaps between all these DNA fragments. This includes all of those Okazaki fragments as well as the little pieces of DNA from where the RNA primers were replaced.

If you review the steps of DNA replication, you will see that each parent strand served as a template for a complementary daughter strand. Each new strand consists of one newly-synthesized strand and one strand inherited directly form the parent. This is known as being semi-conservative because it is 50% original, template DNA and 50% newly-synthesized DNA.

Please note that this process is not perfect and can sometimes result in mistakes while copying, leading to mutations in the DNA.

"During replication, the yin-yang strands of DNA were peeled apart. The yin was used as a template to create a yang, and the yang to make a yin—and this resulted in two yin-yang pairs" (The Gene: An Intimate History by Siddhartha Mukherjee)

Next: Gene Expression

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DNA Structure & Replication

Table of Contents

Reviewing Nucleotides

A. Nucleotide Structure