The structure of DNA

Working out the structure

No single person discovered DNA. Its story is a chain of clues collected over about 85 years.

• 1869: Swiss doctor Friedrich Miescher extracted a new phosphorus-rich substance from the nuclei of white blood cells in pus-soaked bandages. He called it "nuclein". We now call it deoxyribonucleic acid, DNA.
• Early 1900s: Russian-American chemist Phoebus Levene showed that DNA is made of units containing a sugar (deoxyribose), a phosphate group and one of four bases. He named these units nucleotides. He wrongly thought DNA was too simple to carry genetic information.
• 1944 and 1952: Experiments by Oswald Avery's team with bacteria, and by Alfred Hershey and Martha Chase with viruses, showed that DNA, not protein, carries inherited information.
• 1950: Erwin Chargaff measured the bases in DNA from many species. The amounts varied between species, but in every sample the amount of adenine equalled thymine and guanine equalled cytosine. These are Chargaff's rules.
• 1951–1952: At King's College London, Rosalind Franklin and her PhD student Raymond Gosling fired X-rays at fibres of DNA. In May 1952 they took an exceptionally clear image, Photo 51. Its X-shaped pattern showed DNA is a helix, and Franklin's measurements gave its width and the distance between turns. She also worked out that the phosphate backbones are on the outside.
• 1953: Linus Pauling, the most famous chemist of the day, published a three-stranded model with the bases on the outside. It was wrong. In January 1953 Maurice Wilkins, who worked in the same lab as Franklin, showed Photo 51 to James Watson without her knowledge. Watson and Francis Crick in Cambridge combined Franklin's data, Chargaff's rules and cardboard models of the bases, and in April 1953 published the double helix.

Watson, Crick and Wilkins shared the 1962 Nobel Prize. Franklin had died of ovarian cancer in 1958, aged 37, and Nobel Prizes are not awarded after death. For decades her role was played down. Historians now see the double helix as a discovery that depended on her data, and it is a reminder that science is a collaborative process in which credit is not always shared fairly.

Nucleotides and the double helix

DNA is a polymer: a long chain of repeating units called nucleotides. Each nucleotide has three parts:

• a phosphate group
• a sugar called deoxyribose (a ring of five carbon atoms)
• a nitrogen-containing base: adenine (A), thymine (T), guanine (G) or cytosine (C).

The sugar of one nucleotide bonds to the phosphate of the next, forming a strong sugar–phosphate backbone. Two of these strands wind round each other to form a double helix, like a twisted ladder. The backbones are the sides of the ladder and pairs of bases are the rungs.

The bases are held together by weak hydrogen bonds and always pair the same way. This is complementary base pairing:

• A pairs with T, held by two hydrogen bonds
• G pairs with C, held by three hydrogen bonds.

The reason is shape. A and G are large bases with two rings (purines); T and C are smaller with one ring (pyrimidines). A large base always pairs with a small one, so every rung is the same width, about 2 nanometres. And only A–T and G–C line up their hydrogen bonds properly. That explains Chargaff's rules: every A has a T opposite it, so the amounts must be equal.

The two strands run in opposite directions. Chemists number the carbons in the sugar, and one end of each strand is called the 5′ end ("five prime") and the other the 3′ end. One strand runs 5′ to 3′ top to bottom; its partner runs 5′ to 3′ bottom to top. We say the strands are antiparallel.

How DNA copies itself

Before a cell divides it must copy all its DNA, so each new cell gets a complete set. The base-pairing rule makes this possible. Watson and Crick spotted it in their first paper: if you know one strand, you know the other.

1. An enzyme called helicase breaks the weak hydrogen bonds between the bases and unzips the double helix.
2. Each old strand acts as a template. Free nucleotides floating in the nucleus pair with the exposed bases: A with T, G with C.
3. The enzyme DNA polymerase joins the new nucleotides together to make a new backbone. It can only add nucleotides to the 3′ end of a growing strand, so on one side the new strand is built in short pieces that are joined afterwards.
4. The result is two identical DNA molecules. Each has one old strand and one new strand, so replication is called semi-conservative.

DNA polymerase is astonishingly accurate. It "proofreads" as it goes, and other enzymes repair mistakes afterwards, so only about one wrong base gets through for every billion copied. A human cell copies about 6 billion base pairs every time it divides, so even so, each new cell carries a handful of new changes. Those rare errors are one source of mutations (1E).