state that the bases adenine and guanine are purines with a double ring structure, and that the bases cytosine, thymine and uracil are pyrimidines with a single ring structure (structural formulae for bases are not expected)

Structure of Nucleic Acids and DNA Replication (Cambridge AS & A Level – Topic 6)

Learning Objective

State that adenine (A) and guanine (G) are purines with a double‑ring structure, and that cytosine (C), thymine (T) and uracil (U) are pyrimidines with a single‑ring structure. Explain how this classification, together with the sugar‑phosphate backbone, underpins DNA double‑helix geometry, base‑pairing, semi‑conservative replication and the flow of genetic information.

Key Definitions

• Purine: nitrogenous base containing two fused carbon‑nitrogen rings.
• Pyrimidine: nitrogenous base containing a single carbon‑nitrogen ring.
• Deoxyribose: five‑carbon sugar of DNA nucleotides (lacks a 2’‑OH).
• Ribose: five‑carbon sugar of RNA nucleotides (has a 2’‑OH).
• Phosphodiester bond: covalent link joining the 3’‑hydroxyl of one sugar to the 5’‑phosphate of the next.
• Antiparallel strands: the two DNA polynucleotide chains run in opposite directions (5’→3’ opposite 3’→5’).
• Semi‑conservative replication: each daughter DNA molecule contains one original (parental) strand and one newly synthesised strand.

Classification of DNA & RNA Bases

DNA vs. RNA – Key Structural Differences

• DNA nucleotides contain deoxyribose; RNA nucleotides contain ribose (2’‑OH present).
• DNA uses thymine (T) as a pyrimidine; RNA replaces thymine with uracil (U).
• Both DNA and RNA share the same set of purine (A, G) and pyrimidine (C, T/U) bases, but the sugar and the presence/absence of thymine distinguish them.

DNA Double‑Helix Structure & Base‑Pairing

• Two antiparallel strands are linked by phosphodiester bonds to form a sugar‑phosphate backbone.
• Base‑pairing is highly specific:

  • Adenine (A) ↔ Thymine (T) – 2 hydrogen bonds.
  • Guanine (G) ↔ Cytosine (C) – 3 hydrogen bonds.
  • In RNA, Adenine pairs with Uracil (U) instead of Thymine.

• Each purine (double‑ring) always pairs with a pyrimidine (single‑ring), keeping the helix width uniform.

Semi‑Conservative DNA Replication

1. Origin of replication – AT‑rich DNA sequence where the replication process is initiated.
2. Helicase – unwinds the double helix, creating a replication fork.
3. Single‑strand‑binding (SSB) proteins – stabilise the separated strands.
4. Primase – synthesises a short RNA primer (5’→3’) on each template strand.
5. DNA polymerase (main synthesis enzyme) – adds deoxyribonucleotides complementary to the template strand, extending the new strand in the 5’→3’ direction.

   • Leading strand – synthesised continuously towards the fork.
   • Lagging strand – synthesised discontinuously as Okazaki fragments away from the fork.

6. DNA polymerase I (or RNase H) – removes RNA primers and fills the resulting gaps with DNA.
7. DNA ligase – joins adjacent Okazaki fragments, producing an uninterrupted phosphodiester backbone.

Transcription – From DNA to mRNA (Eukaryotic)

• Occurs in the nucleus (or nucleoid in prokaryotes).
• RNA polymerase binds to the promoter region and synthesises a single‑stranded precursor mRNA (pre‑mRNA) in the 5’→3’ direction, using the template strand as a guide. The opposite strand is the coding (non‑transcribed) strand and has the same sequence as the mRNA (except T→U).
• mRNA processing (eukaryotes):

  • 5’‑capping – addition of a modified guanine nucleotide.
  • Splicing – removal of non‑coding introns and joining of exons.
  • Poly‑A tail – addition of a stretch of adenine nucleotides to the 3’ end.

  The mature mRNA is then exported to the cytoplasm for translation.

Translation – From mRNA to Protein

• Occurs on ribosomes in the cytoplasm (or on the rough ER).
• Key components:

  • Ribosome – site of peptide‑bond formation; consists of a large and a small subunit.
  • Codons – groups of three nucleotides on mRNA that specify an amino acid.
  • Transfer RNA (tRNA) – carries a specific amino acid and possesses an anticodon complementary to the mRNA codon.
  • Start codon (AUG) – signals the beginning of translation and codes for methionine.
  • Stop codons (UAA, UAG, UGA) – terminate translation.

• The linear sequence of codons determines the linear sequence of amino acids in the polypeptide chain.

Gene Mutations and Their Effects

Example – Missense mutation: In sickle‑cell disease a single A→T substitution in the β‑globin gene changes the codon from GAG (glutamic acid) to GTG (valine). The resulting haemoglobin protein polymerises under low‑oxygen conditions, distorting red blood cells.

Link to Protein Synthesis (Topic 6.2)

The linear order of nucleotides in DNA encodes the sequence of amino acids in a protein. Through transcription (DNA → pre‑mRNA → mature mRNA) and translation (mRNA → polypeptide), the genetic code is read in codons, each specifying a particular amino acid, thereby converting genetic information into functional proteins.