Structure of DNA and RNA, and DNA packaging

Nucleotides and the polynucleotide chain

DNA and RNA are long chains of nucleotides. Each nucleotide has a nitrogenous base, a pentose sugar and a phosphate group. The bases are purines (adenine, guanine) and pyrimidines (cytosine, thymine in DNA, uracil in RNA). A base joins the 1′ carbon of the sugar by an N-glycosidic linkage to form a nucleoside. A phosphate joins the 5′-OH of the sugar by a phosphoester linkage to form a nucleotide. Nucleotides join by 3′-5′ phosphodiester linkages into a chain. One end has a free phosphate (5′ end); the other has a free -OH (3′ end). Sugar and phosphate form the backbone, and the bases stick out from it. In RNA, the sugar is ribose, with an extra -OH at the 2′ position, and uracil replaces thymine (thymine is 5-methyl uracil).

Watson and Crick's double helix (1953): key features

• Based on X-ray diffraction data from Maurice Wilkins and Rosalind Franklin.
• Two polynucleotide chains, with the sugar-phosphate backbone outside and the bases inside.
• The chains are antiparallel: one runs 5′→3′, the other 3′→5′.
• Bases pair by hydrogen bonds: A with T (two bonds) and G with C (three bonds). A purine always faces a pyrimidine, so the strands stay a uniform distance apart.
• The two chains coil in a right-handed helix. Pitch 3.4 nm, about 10 bp per turn, 0.34 nm between base pairs.
• Base pairs stack over one another; this, with the hydrogen bonds, keeps the helix stable.
• The strands are complementary: knowing one gives the other. This hinted at how DNA could be copied.

DNA vs RNA: structure

Chargaff's rule and base pairs

Packaging DNA into the nucleus

Human DNA in one diploid cell is about **2.2 m** long, but the nucleus is only about **10⁻⁶ m** across. So DNA must be packed very tightly.

1. 1
   Prokaryotes (e.g. E. coli) have no nucleus. Their negatively charged DNA is held by positively charged proteins as large loops in the nucleoid.
2. 2
   Eukaryotes use histones: positively charged, basic proteins rich in lysine and arginine.
3. 3
   Eight histone molecules form a histone octamer.
4. 4★
   Negatively charged DNA wraps around the positively charged octamer to form a nucleosome, holding about 200 bp of DNA.
5. 5
   Nucleosomes repeat along the DNA like 'beads on a string' under the electron microscope. This thread is chromatin.
6. 6
   Chromatin coils further and condenses into chromosomes at metaphase. This higher packing needs non-histone chromosomal (NHC) proteins.
7. 7
   Loosely packed, lightly stained, active chromatin is euchromatin; densely packed, darkly stained, inactive chromatin is heterochromatin.

★ key step

How to draw the DNA double helix and a nucleosome

• Draw two ribbons twisting around each other as a right-handed helix. Label them sugar-phosphate backbone.
• Draw short rungs between them and label base pairs; write A=T on one and G≡C on another.
• Mark 5′ and 3′ at the top and bottom of each strand, in opposite directions (antiparallel).
• Mark one full turn as pitch 3.4 nm and the gap between two rungs as 0.34 nm.
• For the nucleosome, draw a small cylinder labelled histone octamer with a DNA line wound around it. Label the DNA and the linker DNA that runs on to the next nucleosome.