6. What DNA Is (1,149) DONE

In this chapter, we focus on what DNA is--its structure--before turning to what it does.

It is said that structure determines function and DNA embodies this. When the structure of DNA was discerned by James Watson and Francis Crick (with key x-ray crystallographic data supplied by Rosalind Franklin), they understood immediately how it would function.

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 suggested, which included nucleotide base pairing, revealed to them how one of DNA's primary functions, replication, could work. This will become clearer shortly.

Structure of DNA

At its core, DNA is a beautifully simple idea: a long string of letters, paired in a way that allows it to be copied.

I discussed the structure of DNA briefly in an earlier chapter. Let me quickly review that to bring us back up to speed. Then I'll expand on it.

Recall that I said a strand of DNA is a type of molecule called a polymer. In other words, it's a chain of repeating subunits generically called monomers. The monomer subunits of DNA are four different nucleotides. And, since DNA is a double helix, it's really two polymers twisted around each other and weakly connected to each other in the middle.

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.

Before we go any further, let's 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 right down the middle so we're left with two separated DNA strands.

Both of these polymers are strings of nucleotides. So it's time to look at a nucleotide in more detail.

A nucleotide has three parts: a sugar (deoxyribose), a phosphate, and one of the four different bases.

The sugar and the phosphate of every nucleotide contributes to what is referred to simply as the sugar-phosphate backbone. These are the rails of the ladder.

The sugar-phosphate backbone provides the molecule's structure, but it doesn't contain information. It doesn't encode anything. It primarily supports and positions the third component of the nucleotide, the base, to pair with the base from the other strand. 

In contrast, each full rung of the ladder is made of two bases sticking inward from their respective sugars. This is the variable part of the nucleotide. The order of the bases in a DNA strand represents the molecule's coded information.

The two bases across from each other--that is, the two that extend inward from the sugar-phosphate backbone--are connected in the middle via weak chemical bonds called hydrogen bonds.

It is important that these two strands be attached to each other. Otherwise the double helix wouldn't stay intact. It's equally important that the bonds are weak, because during both replication and transcription (gene expression) the two strands must be separated from each other.

Four bases

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

As a rule, the rungs of the ladder must be composed of the bases of two complementary nucleotides. 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. Non-complementary nucleotides do not.

In other words, 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.

It also 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.

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.

The second base in our example sequence is a C. Thus, the second base on its complement strand must be G.

Two more points

One more thing about complementary nucleotides: when they are paired, the A base and the T base are connected with two hydrogen bonds. But three hydrogen bonds form between G and C. Thus, 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 will also be important when we discuss replication: 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 started with a perfect wooden ladder, sawed it right down the middle, turned one of the rails upside down and then reconnected the rungs.

To distinguish the two orientations, scientists used the numbered carbons in the deoxyribose sugar. Doing that resulted in naming one of the strands 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 each of 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 of the double helix are complementary, but the two DNA molecules of the helix run in opposite directions.

We now understand what DNA is. In the next chapter, we turn to what it does--and how this simple structure makes life possible.