6. What DNA Is (896;7/31)

At first glance, DNA doesn’t look like much--a long, repetitive chain made of just four kinds of parts. And yet, this simple structure is capable of both storing an enormous amount of information and replicating itself with incredible accuracy.

Structure shapes function, and DNA is a clear example. When the structure of DNA was discovered by James Watson and Francis Crick and with key x-ray crystallographic data supplied by Rosalind Franklin, they understood immediately how it worked.

In their seminal 1953 article in the scientific journal Nature, they wrote, cheekily: "It has not escaped our notice that the specific (base) pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." In other words, the structure they proposed, which included base pairing, revealed right away to them how one of DNA’s primary functions--replication--could work.

Structure of DNA

At its core, DNA is beautifully simple. Recall that it's a polymer, which means it's a chain of repeating subunits that are generically called monomers. DNA being a double helix, it's really two polymers twisted around each other and weakly connected in the middle. The monomers of DNA are four different molecules called DNA nucleotides.

Let's mentally untwist our double helix ladder so it looks like a real ladder with two side rails and rungs between them. Now let's cut the rungs down the middle so we're left with two separated DNA strands, each just a long chain of DNA nucleotides.

Zooming in on a nucleotide, it essentially has two parts: a backbone component that will comprise the rails of the ladder, and one of four different bases that will make up the rungs. The backbone gives the molecule structure. It supports and positions the bases so they can pair with their partners on the other strand. It is the bases--not the backbone--that contain the genetic code.

Each full rung of the ladder is actually made of two bases sticking inward from the backbones of the two strands. These two bases are joined in the middle by relatively weak chemical bonds. The two strands must be attached to each other or the double helix wouldn't stay intact. But it's important that the bonds be weak, because during many cell processes like DNA replication, repair and transcription, the two strands must be temporarily separated.

Four bases

The four kinds of DNA nucleotides are defined by their four different possible bases. We usually refer to nucleotides by the first letter of the name of their base: A (adenine), G (guanine), C (cytosine) and T (thymine).

The rungs of the ladder are composed of the bases of two complementary DNA nucleotides. A is complementary to T and C is complementary to G. The bases of complementary nucleotides fit together nicely when paired. Non-complementary bases don’t fit properly or form stable pairs.

So based on their chemical shapes, a rung can consist of an A base extending inward from one of the rails and a T extending inward from the other the rail. Or a rung can consist of a G and a C. A rung cannot consist of a G and a T.

Also, it doesn't matter which of the two strands 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.

The key point is simple: each base determines what must sit across from it. That simple pairing rule means that if the two strands are ever separated, each one contains the information needed to rebuild its partner.

A quick exercise

Try this before reading on. Consider a small piece of DNA in which the order of the nucleotide bases is ACCTGTGCAA. This DNA strand is made of 10 nucleotides (a "10-mer") with the order of the nucleotide bases as shown.

The exercise: What would be the code on the opposite strand? (Hint: replace each base with its complementary partner)

If you said "TGGACACGTT" you'd be right. If A 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.

Antiparallelism

One last but very important point. The double helix is like a twisted ladder, but it's a modified twisted ladder. This is because the two rails run in opposite directions. It's as if we started with a perfect wooden ladder, sawed it down the middle, turned one of the rails upside down and then reconnected the rungs.

To distinguish the two rail orientations, scientists used the numbered carbons in the sugar that's part of the backbone--specifically the 5′ and 3′ positions where nucleotides link together.

The underlying chemistry doesn't matter. Just know that one of the strands is called 5'-to-3' ("five prime to three prime") and the other 3'-to-5' ("three prime to five prime"). This is how we'll refer to the strands once we get into genome replication. The fact that the rails are anti-parallel doesn't change the fact that the two strands contain complementary bases.

Antiparallelism may seem like a small detail, but it will matter enormously when we discuss genome replication.

We now understand what DNA is. In the next chapter, we turn to what it does--and how a simple sequence of nucleotides can be used to build proteins.