DNA & RNA: Structure, Replication & the Genetic Code

Nucleotide Structure: The Molecular Building Block

All nucleic acids are polymers built from nucleotide monomers. Each nucleotide contains three covalently bonded components:

• Pentose sugar — deoxyribose (in DNA) or ribose (in RNA). The only structural difference is that ribose carries a hydroxyl (–OH) group at the 2' carbon, whereas deoxyribose has only a hydrogen (–H) there.
• Phosphate group — a negatively charged PO₄³⁻ group attached to the 5' carbon of the sugar. This gives the backbone its strong negative charge and is the site of covalent linkage between adjacent nucleotides (phosphodiester bonds).
• Nitrogenous base — attached to the 1' carbon of the sugar. Bases are grouped as purines (double-ring: adenine A, guanine G) or pyrimidines (single-ring: cytosine C, thymine T in DNA; uracil U replaces thymine in RNA).

Nucleotides polymerise via condensation reactions (releasing water), forming a phosphodiester bond between the 3'–OH of one sugar and the 5'–phosphate of the next. This creates a directional backbone with a free 5'–phosphate at one end and a free 3'–OH at the other — the strand is said to run 5' → 3'.

Applied example: A question might show a partial nucleotide sequence and ask you to identify whether it is DNA or RNA. Look for the base U (uracil) — its presence confirms RNA. If only A, T, C, G appear, it is DNA. If asked to draw a nucleotide, remember to show all three components connected correctly: phosphate to 5' carbon, base to 1' carbon.

DNA Double Helix: Structure and Base Pairing

The DNA molecule is a double-stranded helix, first described by Watson and Crick in 1953 using X-ray crystallography data (primarily from Rosalind Franklin). Its key structural features are:

• Antiparallel orientation — the two strands run in opposite directions. One runs 5' → 3' and its complement runs 3' → 5'. This antiparallel arrangement is essential for replication and transcription enzymes, which can only read and synthesise in one direction.
• Complementary base pairing — bases on opposite strands hydrogen-bond in a specific, fixed way: A pairs with T (2 hydrogen bonds) and G pairs with C (3 hydrogen bonds). The G≡C bond is stronger; organisms or DNA regions with high G-C content require more energy to denature.
• Sugar-phosphate backbone — the alternating deoxyribose and phosphate groups form the outer 'rails' of the helix; the bases stack inward, hydrophobically stabilising the structure.
• Major and minor grooves — the helical twist creates two grooves of different widths. Transcription factors and regulatory proteins often bind in the major groove, where base-specific contacts are possible.

DNA is condensed by wrapping around histone proteins to form nucleosomes, then further coiled into chromatin. During cell division, chromatin is maximally condensed into visible chromosomes.

Applied example (Chargaff's rules): If a DNA molecule is 22% thymine, what percentage is guanine? Because A = T and G = C, and all percentages sum to 100%: A = T = 22%, so A + T = 44%, leaving G + C = 56%, meaning G = C = 28%. VCAA short-answer questions frequently test this logic — practise applying it quickly.