8. What DNA Is

Let's focus in this chapter on the structure of DNA--what DNA is. In the next, I'll cover how DNA functions--what it does. Structure and function work hand-in-hand. The old saw is "structure determines function." That's a bit of an oversimplification, but it is clearly the case with respect to DNA.

In fact, when the structure of DNA was discovered by James Watson and Francis Crick (with key x-ray crystallographic data supplied by Rosalind Franklin), they knew immediately how it would function. In their seminal paper, they wrote, cheekily: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." In other words, the structure they proposed (the base pairing) instantly communicated how one of its key functions (replication) could work. We'll see this clearly by the time we finish the next chapter.

If we simplify and say that proteins are about action, then we can also say that DNA--specifically the sequence of bases in the double helix--is about information. 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 every job in the factory is performed. I'll stick with that 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 loosely thought of as the cell's control center. Genomic DNA (except for the relatively small amount of DNA in mitochondria) remains sequestered inside the nucleus with one exception: during cell division, or mitosis, the nuclear membrane breaks down to allow the DNA strands to be pulled into one or the other of the new cells (or "daughter cells"). Otherwise the DNA originals of the SOPs remain where they should be: protected in a the nuclear vault.

I briefly introduced DNA in an earlier chapter. Let me review that quickly and then expand on it. I said that DNA is a type of molecule called a polymer. A polymer ("poly-" means "many") is a long molecule made of a linear arrangement of smaller molecule subunits that are generically called "monomers"("mono-" meaning "one"). Most of the cell's macromolecules are polymers. Proteins and DNA are. And carbohydrates can be polymers.

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 specific monomer subunits of DNA polymer are nucleotides. So we can say that a DNA molecule is a long lineup of nucleotides connected to each other.

The DNA double helix is like a twisted ladder, an analogy I'll be using throughout this chapter. If we untwist the ladder and cut right down the middle of it, each of the two long rails and their respective halves of the rungs represents one DNA polymer. The double helix is two DNA polymers connected in the middle via weak chemical bonds (hydrogen bonds).

The long rails of the ladder are DNA's "sugar-phosphate backbone." Each nucleotide monomer added to the chain contributes one sugar and one phosphate to the rail. The sugar-phosphate background is obviously essential to the molecule's structure, but no coded information is contained it. It simply repeats on and on.

In contrast, each full rung of the ladder is made of two bases sticking inward from their respective sugars. These are the variable parts of the two nucleotide monomers lying across from each other. The order of the bases in the DNA molecule represents the molecule's coded information.

There are four kinds of nucleotides defined by the four different bases in DNA. 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").

A hard and fast rule of DNA: each rung of a double helix ladder must be composed of the bases of two complementary nucleotides. More precisely, A is complementary to T and C is complementary to G. The bases of complementary nucleotides fit together nicely when paired across from each other.

In other words, 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 other the rail. Or a rung can consist of a G and a C. But a rung cannot consist of a G and a T. The shape of the G doesn't fit well with the shape of the T.

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 the 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 as I show. Next, I could ask what the code of the opposite strand would be in the context of a double helix. Take a moment before reading on.

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 must be a T across from it on the other. The second base in our example sequence is a C. Thus, the second base on its complement strand must be G. Just remember: A goes with T, and G goes with C.

One more thing about complementary nucleotides: Two hydrogen bonds connect the A base and the T base when they are paired, or across from each. But three hydrogen bonds form between G and C. This in part explains why it is easier to pull an A away from a T than to pull a G away from a C. This property of DNA will become relevant later when we discuss replication.

One final structural concept: anti-parallelism. It's not as complicated as it sounds. It turns out that, yes, the double helix is like a twisted ladder, but it is a modified twisted ladder in that the two rails run in opposite directions. It's as if we had a perfect wooden ladder, sawed it right down the middle, turned one of the rails upside down and then reconnected the rungs.

The fact that the rails are anti-parallel doesn't change the fact that the two polymers of the double helix are complementary, but the two DNA molecules of the helix run in opposite directions. This, too, will become relevant later because the enzyme that replicates the DNA (DNA polymerase) can only read the genetic code in one of the two directions.

On to DNA function: how it works!