• DNA Replication is semi-conservative — each new DNA molecule keeps one original strand and builds one brand-new strand.
• Helicase unwinds/unzips the double helix; DNA polymerase builds new strands from free nucleotides; DNA ligase joins fragments together.
• Because DNA polymerase only works 5'→3', one new strand (leading) is made continuously, the other (lagging) is made in chunks called Okazaki fragments.
• Meselson & Stahl's nitrogen-isotope experiment proved replication is semi-conservative, not conservative.
• The genetic code is a triplet code: 3 DNA bases = 1 codon = 1 amino acid. It is non-overlapping, degenerate, and universal.
• A gene is a sequence of DNA bases that codes for one polypeptide (Crick's Central Dogma: DNA → RNA → Protein).
• Transcription (in the nucleus): the antisense/template DNA strand is copied into a single-stranded mRNA molecule by RNA polymerase.
• Translation (in the cytoplasm, at the ribosome): tRNA molecules match their anticodons to mRNA codons, delivering amino acids that are joined by peptide bonds into a polypeptide.

Why does DNA need to be copied at all?

Think of DNA as the master instruction manual for building and running a cell. Before a cell splits into two (mitosis), both new "daughter" cells need their own complete, identical copy of that manual — otherwise one daughter cell would be missing pages of instructions. So before division, the cell doubles its DNA. This copying process is called replication, and it happens during the S phase of interphase (i.e. before the cell is actually dividing — not during mitosis itself).

Semi-conservative replication — the "half kept, half new" rule

DNA is a double helix — picture it like a zip, with two strands running antiparallel to each other, held together by hydrogen bonds between complementary bases (A–T and C–G). When it's time to replicate:

1. The helix is "unzipped" down the middle — the two original strands separate.
2. Each of these two original strands is used as a template to build a brand new complementary strand alongside it.
3. You end up with two complete double helices — but each one is made of one old (original) strand + one new strand.

This is why it's called semi-conservative: "semi" = half. Half of each new DNA molecule (one whole strand) is conserved from the original, and the other half is freshly synthesised.

Why does it matter that one original strand is kept?

Keeping one original strand in every new DNA molecule ensures genetic continuity — new cells produced by division inherit exactly the same genes as their parent cell. Since cells in our bodies are constantly being replaced (skin, blood, gut lining, etc.), and cells also divide during growth, this is essential: the replacement cells need to carry out exactly the same functions as the ones they're replacing.

The machinery of replication, step by step

Leading strand vs lagging strand — the tricky bit

Here's the twist that catches most students out: DNA polymerase can only add new nucleotides in one direction — building the new strand 5' to 3'. But the two original template strands run in opposite directions to each other (they're antiparallel). This creates a problem at the "replication fork" (the Y-shaped point where the helix is splitting open):

• Leading strand: DNA polymerase attaches to the 3' end of the template and moves towards the replication fork continuously — as fast as the helix unzips, the new strand is built in one smooth, unbroken run.
• Lagging strand: on the other template strand, DNA polymerase has to move away from the replication fork (5' → 3' on the new strand still, but relative to the fork this means working "backwards"). It can only build in short bursts called Okazaki fragments, which then need to be stitched together afterwards by DNA ligase.

   3'━━━━━━━━━━━━━━━━━━► 5'   (original strand — LEADING template)
   5'◄━━━━━━━━━━━━━━━━━━ 3'   (original strand — LAGGING template)
                    ▲
             replication fork
                    
   Leading strand: built continuously, chasing the fork
   Lagging strand: built in short Okazaki fragments,
                   later joined by DNA ligase
    

Evidence: Meselson & Stahl's Experiment

Before the 1950s, scientists weren't sure whether DNA replication was conservative (the whole original molecule stays intact and an entirely new molecule is made separately) or semi-conservative. Matthew Meselson and Franklin Stahl settled the debate using a clever isotope-tracking experiment.

The experiment, step by step

1. Bacteria were grown in broth containing only the heavy nitrogen isotope, ¹⁵N. Since DNA bases contain nitrogen, over many generations all the bacterial DNA became labelled with ¹⁵N only.
2. A sample of this ¹⁵N DNA was spun in a centrifuge — it settled near the bottom of the tube (heavy DNA is denser).
3. The ¹⁵N-bacteria were then transferred into broth containing only the light isotope, ¹⁴N, and allowed exactly one round of DNA replication before their DNA was extracted and centrifuged again.

The actual result: after one round of replication in the light broth, all the DNA settled in the middle of the tube — a single intermediate-density band. This confirmed every molecule was now a 50/50 mix of heavy and light nitrogen, exactly as semi-conservative replication predicts. (If you let replication run for further rounds, the ratio of ¹⁵N:¹⁴N strands goes from 1:1 after round one, to 3:1 after round two, to 7:1 after round three — always leaving some detectable heavy DNA, because the original strands never disappear, they just get diluted among more and more new strands.)

The triplet code

DNA only has four "letters" in its alphabet — the bases A, T, C and G (or A, U, C, G in RNA). But proteins are built from 20 different amino acids. Four letters obviously can't code for 20 things one-to-one, so cells use a triplet code: every group of three consecutive bases (called a codon) codes for one amino acid.

For example: CAG codes for valine, TTC codes for lysine, GAC codes for leucine, CCG codes for glycine. (You don't need to memorise specific codon-to-amino-acid pairings for the exam — just understand the principle of the triplet code.)

Three defining properties of the genetic code

① Non-overlapping

Each base is read only once, as part of just one codon. The sequence is read in consecutive, non-overlapping chunks of three — a base can't be "shared" between two different codons. So AUGCGU is read as AUG | CGU — never as AUG, UGC, GCG... (which would be overlapping).

② Degenerate

With 4 bases and a triplet code, there are 4³ = 64 possible codons — but only 20 amino acids that commonly occur in proteins. That means most amino acids are coded for by more than one codon. This "extra" redundancy is what "degenerate" means here — it's not a negative word in this context, it just means there's more than one way to spell the same amino acid.

③ Universal

With only a few rare exceptions, every living organism uses the same genetic code — the same triplet codes for the same amino acid whether you're looking at a bacterium, a sunflower, or a human. This is exactly why genetic engineering is possible: you can take a gene from one species and insert it into a completely different species, and the recipient's cellular machinery will still read and translate it correctly, because they're all "speaking the same language."

Crick's Central Dogma

A gene is a sequence of nucleotides that forms part of a DNA molecule — and a single DNA molecule contains many genes strung along its length, like many separate paragraphs within one long book. Each gene's specific sequence of bases codes for the production of one specific polypeptide (protein).

Proteins are chains of amino acids bonded together, and it's the exact order of these amino acids (called the protein's primary structure) that determines how the protein folds up and, ultimately, what it does. So genes control protein structure — and therefore protein function — because they dictate precisely which amino acids get joined together, and in what order, during protein synthesis.

  CELL
   └─ NUCLEUS
       └─ CHROMOSOME
           └─ DNA molecule
               └─ GENE (specific sequence of nucleotides)
                     │
                     │  transcription + translation
                     ▼
               PROTEIN MOLECULE (polypeptide)
                     = chain of AMINO ACIDS
    

Protein synthesis happens in two stages: transcription, then translation. Transcription is stage one, and it happens inside the nucleus.

What is mRNA, and why is it needed?

DNA is far too precious and important to leave the nucleus — it's the master copy, and it needs to stay safe. So instead, the cell makes a disposable "working copy" of just the one gene it needs, in the form of a molecule called messenger RNA (mRNA). mRNA is single-stranded (unlike double-stranded DNA) and is built from RNA nucleotides. Its job is simply to carry the genetic information encoded in that gene out of the nucleus and over to a ribosome, where it can actually be used to build a protein.

The process of transcription, step by step

1. Part of the DNA molecule unwinds and "unzips" — the hydrogen bonds between complementary base pairs break, exposing the gene that needs to be transcribed.
2. The enzyme RNA polymerase moves along one of the two exposed DNA strands, catalysing the whole process.
3. Free, activated RNA nucleotides pair up (via hydrogen bonding) with their complementary bases on this exposed strand of DNA.
4. RNA polymerase joins the sugar-phosphate groups of these RNA nucleotides together, forming the sugar-phosphate backbone of the new mRNA strand.
5. Once the gene has been fully transcribed, the hydrogen bonds between the mRNA and the DNA template break, and the original double-stranded DNA molecule zips back up (reforms).
6. The finished mRNA molecule leaves the nucleus through a pore in the nuclear envelope, heading for a ribosome in the cytoplasm.

Sense strand vs antisense strand — which one actually gets copied?

Only one of the two DNA strands is used as the template for building mRNA:

  DNA sense strand:        5'-A T G C C G C A-3'
  DNA antisense/template:  3'-T A C G G C G T-5'   ← RNA polymerase reads this
                                     │
                                     ▼  (complementary base pairing, T→U)
  mRNA:                    5'-A U G C C G C A-3'   ← identical to sense strand, but U instead of T
    

Translation is stage two of protein synthesis, and it happens in the cytoplasm, at a ribosome — a striking contrast to transcription, which happens in the nucleus. This is one of the most commonly tested facts in this whole chapter, so lock it in.

Meet tRNA — the delivery driver of the cell

Floating around in the cytoplasm are molecules of transfer RNA (tRNA) — small, single-stranded RNA molecules that fold up into a distinctive clover-leaf shape. Each tRNA molecule has two important functional parts:

• An anticodon — a triplet of unpaired bases at one end that can pair with a complementary codon on mRNA.
• An amino acid binding site at the other end, where one specific amino acid attaches.

There are roughly 20 different tRNA molecules, each with its own specific anticodon and its own specific amino acid that it's designed to carry. Think of each tRNA as a delivery driver who only ever delivers one particular type of parcel (amino acid) to one particular type of address (its matching mRNA codon).

The process of translation, step by step

1. After leaving the nucleus, the mRNA molecule attaches to a ribosome in the cytoplasm.
2. Near the start of the mRNA sits the start codon, AUG — this signals where translation should begin, and codes for the amino acid methionine.
3. A tRNA molecule with the complementary anticodon (UAC) — carrying methionine — binds to this start codon via hydrogen bonds.
4. A second tRNA molecule then binds to the next codon along, bringing its own amino acid. Two tRNA molecules sit on the ribosome side-by-side at any one moment.
5. A peptide bond forms between the two amino acids via a condensation reaction.
6. The ribosome shifts along the mRNA (moving in the 5'→3' direction) by one codon, the first (now "empty") tRNA is released, and a third tRNA binds to the next codon, bringing the next amino acid.
7. This cycle repeats — codon by codon — steadily building up a growing chain of amino acids.
8. The process continues until the ribosome reaches a stop codon on the mRNA. Stop codons don't code for any amino acid — they simply signal that translation is complete, triggering the release of the finished polypeptide chain.

  mRNA:      5'-AUG-UAU-AAA-...-UAA-3'
              │    │    │        │
  codon:     AUG  UAU  AAA      UAA (STOP)
              │    │    │
  anticodon: UAC  AUA  UUU
              │    │    │
  tRNA:      Met—Tyr—Lys ── growing polypeptide chain
    

• I can explain what "semi-conservative replication" means and why it matters.
• I can name the roles of helicase, DNA polymerase, and DNA ligase in replication.
• I can explain the difference between the leading and lagging strands, and why they're synthesised differently.
• I can describe Meselson and Stahl's experiment and explain how its results proved semi-conservative replication.
• I understand the triplet nature of the genetic code and can explain non-overlapping, degenerate, and universal.
• I can explain Crick's Central Dogma (DNA → mRNA → Protein) and what a gene is.
• I can describe the process of transcription step-by-step, including the role of RNA polymerase.
• I can distinguish between the sense (coding) strand and the antisense (template) strand.
• I can describe the process of translation step-by-step, including the roles of codons, anticodons, and tRNA.
• I know that transcription occurs in the nucleus and translation occurs in the cytoplasm.
• I can explain how a peptide bond forms between amino acids during translation.