Nucleic acids. DNA. RNA

At a glance

1. DNA and RNA are chains of nucleotides. Each nucleotide is a base, a five-carbon sugar and a phosphate; phosphodiester bonds join the 3′ carbon of one sugar to the 5′ carbon of the next, so every strand has a 5′ end and a 3′ end.
2. DNA has deoxyribose and the bases adenine (A), guanine (G), cytosine (C) and thymine (T). RNA has ribose, and uracil (U) in place of thymine.
3. DNA is a double helix of two antiparallel strands. A pairs with T by two hydrogen bonds and G with C by three, so one strand's sequence fixes the other's.
4. RNA is usually a single strand that folds onto itself. It carries the code (mRNA), builds ribosomes (rRNA), brings amino acids (tRNA) and regulates genes, and some RNAs are enzymes.
5. RNA's 2′-OH makes it easier to break down than DNA: RNA suits short-lived messages, DNA a lasting store.

01Nucleotides

A nucleotide has three parts:

• a base, a flat ring structure containing nitrogen. The purines, adenine and guanine, have two rings; the pyrimidines, cytosine, thymine and uracil, have one;
• a sugar with five carbons, numbered 1′ to 5′: ribose in RNA, deoxyribose in DNA, which lacks the oxygen on the 2′ carbon;
• one to three phosphates, on the 5′ carbon.

The base is attached to the 1′ carbon by an N-glycosidic bond. A base with its sugar is a nucleoside (adenosine); with phosphates added it is a nucleotide (adenosine monophosphate, AMP). Nucleotides do more than build nucleic acids: ATP and GTP carry energy, cyclic AMP passes on signals inside the cell, and NAD⁺, FAD and coenzyme A all contain an adenine nucleotide.

In a strand, a phosphodiester bond joins the 3′ carbon of one sugar, through a phosphate, to the 5′ carbon of the next. The sugars and phosphates make the backbone and the bases stick out from it. The two ends differ: a free phosphate at the 5′ end, a free 3′-OH at the 3′ end. Sequences are written from 5′ to 3′, the direction in which both DNA and RNA are made, since each new nucleotide is joined to the 3′-OH at the end of the chain. Each phosphate gives up a hydrogen ion, which makes DNA an acid, and is left with a negative charge, which is why DNA binds the positively charged histones that pack it (Chromatin. Nucleosomes).

02The double helix

In 1953 James Watson and Francis Crick proposed the structure of DNA, building on X-ray pictures of DNA fibres taken by Rosalind Franklin and her student Raymond Gosling, and by Maurice Wilkins, and on Erwin Chargaff's finding that DNA holds as much A as T and as much G as C. Watson, Crick and Wilkins shared the 1962 Nobel Prize in Physiology or Medicine; Franklin had died in 1958.

• Two strands wind round each other into a right-handed helix, with the sugar–phosphate backbones outside and the bases stacked inside.
• The strands are antiparallel: one runs 5′ to 3′, the other 3′ to 5′.
• Bases pair by hydrogen bonds: A with T by two, G with C by three. A purine always faces a pyrimidine, so the helix keeps the same width all along.
• The strands are complementary: the sequence of one fixes the other's. Each can serve as the template for a new partner, the basis of DNA replication, and one of them is read when a gene is transcribed.
• Two grooves wind along the helix, a wide major groove and a narrow minor groove. Proteins that bind particular sequences, such as transcription factors, read the edges of the bases mostly in the major groove, without opening the helix.

across the double helix

2nmacross the double helix

from one base pair to the next

0.34nmfrom one base pair to the next

per turn, in solution

10.5base pairsper turn, in solution

in one human set of chromosomes

3.1billion base pairsin one human set of chromosomes

The pairs decide which strands fit together, but stacking, the attraction between neighbouring flat bases piled on one another, does more to hold the helix together. Heated, the strands come apart, which is called melting or denaturation, and the DNA absorbs more ultraviolet light at 260 nm as they do; the temperature at which half of the DNA has separated rises with its share of G–C pairs. Cooled slowly, complementary strands find each other and pair again. Laboratory methods from the polymerase chain reaction to DNA probes rely on this (Basic methods in molecular biology).

The helix Watson and Crick described, B-DNA, is the usual form in cells. Dehydrated DNA takes a wider, shorter form, A-DNA, also the shape of double-stranded RNA and of DNA paired with RNA. Stretches of alternating C and G (CGCGCG) can briefly flip into Z-DNA, a left-handed helix, when the DNA around them is underwound.

Stretched out, the DNA in one human cell, two sets of chromosomes, would be about 2 metres long. A bacterium such as E. coli has one circular chromosome; our nuclear DNA is in 46 linear chromosomes, and each of our mitochondria has one or more copies of a small circular genome of 16,569 base pairs. A closed circle of DNA can twist on itself, supercoiling, and enzymes called topoisomerases add or remove these twists (DNA replication).

03RNA

Three differences set RNA apart from DNA:

• its sugar is ribose, with an OH group on the 2′ carbon;
• it has uracil in place of thymine; uracil pairs with adenine;
• it is usually made as a single strand.

A single strand of RNA folds onto itself: where stretches of its sequence are complementary, they pair into short double helices, closed at one end by a loop (hairpins), and RNA also allows G–U pairs. Hairpins pack into complex three-dimensional shapes, as proteins do, and the shape lets an RNA bind proteins, other RNAs and small molecules, and even catalyse reactions.

RNA molecules that act as enzymes are ribozymes. The ribosome joins amino acids with its rRNA, not its proteins, and some introns cut themselves out of their RNA. Thomas Cech and Sidney Altman, who found the first ribozymes, shared the 1989 Nobel Prize in Chemistry. That RNA can both carry information and catalyse is why the first life is thought to have run on RNA (Origin and evolution of cells).

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1In a sample of double-stranded DNA, 30 per cent of the bases are adenine. What share are guanine?

20 per cent30 per cent40 per cent70 per cent

2What joins one nucleotide to the next in a strand of DNA or RNA?

A hydrogen bond between their basesA phosphodiester bond from the 3′ carbon of one sugar to the 5′ carbon of the nextA peptide bond between their phosphatesA glycosidic bond between their bases

3Two DNA molecules have the same length. Which one separates into single strands at the higher temperature?

The one richer in adenine and thymineThe one with more uracilThe one richer in guanine and cytosineThey melt at the same temperature

4Why is RNA broken down far more easily than DNA?

It has uracil in place of thymineIt is single-stranded, so its bases are exposed to lightIts phosphates carry no chargeThe 2′-OH on its ribose can attack the neighbouring phosphodiester bond and cut the chain

5Zidovudine, an early drug against HIV, is a thymidine analogue with no 3′-OH group. How does it stop the virus copying its genome into DNA?

Once built into the new DNA, it leaves no 3′-OH for the next nucleotide, so the chain endsIt breaks the hydrogen bonds between the strandsIt cuts the viral RNA in twoIt pairs with guanine and causes mutations