DNA Structure

In this "Part I" post I'll be focusing on the structure of DNA--what DNA is. In the next, I'll cover how DNA functions--what it does. First, though, a brief overview of DNA, my favorite molecule!

If proteins are about action, then DNA is about information. Here again, there are many analogies for the role of DNA in a cell. In an earlier post, I likened DNA to a factory's "standard operating procedures," or "SOPs"--that is, the archived instructions that describe how everything in the factory is done. I'll stick with this analogy, even though we'll see in the next post that it has limitations.

Because the DNA is found in the cell's nucleus, the nucleus is considered the cell's control center. The DNA remains sequestered inside the nucleus with one exception: during cell division, or mitosis, the nuclear membrane breaks down to allow the chromosomes to be pulled into one or the other of the new daughter cells. Otherwise the DNA "originals" of the operating instructions remain where they should: protected in a vault (the nucleus).

I briefly introduced DNA in an earlier post. Let me review that. I emphasized in that DNA is a category of molecule called a polymer. Polymers are long molecules made of a linear array of smaller subunit molecules that are generically called "monomers." In fact, most of the cell's macromolecules are polymers. Proteins are polymers. Carbohydrates can be polymers. And DNA is a polymer.

The structure of DNA. Left panel: The double helix is really two DNA polymers twisted around each other and connected in the middle with hydrogen bonds. Middle panel: Complementary base pairing holds (A with T, and G with C). Right panel: The two "rails" of the ladder are made of sugars (dark and light blue pentagons) and phosphates (purple circles). Note that the rails are antiparallel; the dark blue sugar pentagons point up in the left hand rail but the light blue ones point down in the right hand rail.

The monomer subunits of DNA are called nucleotides. So a DNA molecule is just a long stretch of nucleotides lined up and connected to each other. Everyone already knows that DNA is a double helix (see Figure, left panel): it's like a twisted ladder. Each rail and half of the rungs represents one DNA polymer. So the double helix is really two DNA polymers connected in the middle with weak chemical bonds called hydrogen bonds.

The rails of the ladder (see Figure, middle and right panels) are often referred to as DNA's "sugar-phosphate backbone." Each nucleotide monomer contributes one sugar and one phosphate. The fact that the backbone is made of sugars and phosphates is not all that important to us. What's more important are the rungs of the ladder.

Each ladder rung is made up of the variable part of two neighboring nucleotide monomers. The variable part is called the base. There are four kinds of nucleotides, defined by four different bases. We'll make life a little simpler and call those nucleotides by the first letter of their chemical names: A (for "adenine"), G ("guanine"), C ("cytosine") and T ("thymine"). Also notice in the figure (this will become relevant later) that there are two hydrogen bonds between A and T and three between G and C. That means that it wuld be easier to pull the A away from the T than to do the same with G and C.

I'll now introduce a new term. Each rung of a double helix ladder is composed of the bases of two complementary nucleotides. What do I mean by "complementary?" Based on their chemical shapes, a ladder rung can consist of an A base extending inward from one of the rails and a T extending inward from the other. That's because A and T fit together nicely to form a rung. Or a rung can consist of a G and a C. They're also complementary due to their friendly shapes. A rung can't consist of a G and a T. Why? Because the shape of the G doesn't match with the shape of the T. So they can't form a ladder rung.

Also, it doesn't matter which of the two DNA polymers holds which base. A ladder rung can have an A base on one rail and a T to the other. Or it can have the A and T on opposite rails. It only matters that A pairs with T and that G pairs with C.

A quick exercise. Consider a small piece of DNA in which the order of the nucleotide bases is ACCTGTGCAA. That means the DNA strand is made of 10 nucleotides (a "10-mer") with the order of the nucleotide bases being as I showed. Next, I could ask what the code of the opposite strand would be if the strand was in the context of a double helix. Think about it...

If you said "TGGACACGTT" you'd be right! If A always pairs with T, then if we have an A as the first base on one strand, there has to be a T across from it on the other, etc.

There is one more important concept that you must be aware of: anti-parallelism. It's not complicated. It turns out that, yes, the double helix is like a twisted ladder, but it is a modified ladder that has been twisted. The modification is that one of the rails runs in the opposite direction from the other. It is as if I had a wooden ladder, sawed it right down the middle, turned one of the rails on its head and then reconnected the rungs. One rail goes up. The other goes down.

The fact that the rails are anti-parallel doesn't change the fact that the two polymers of the double helix always match each other (A goes with T, and G goes with C), but the two DNA molecules of the helix run in opposite directions. This will be important to appreciate when we broach the topic of genome replication.