1) Big picture: What is DNA and why copy it?

(Image
1 start: “5.4 Replication”)
• Think of DNA as a long two-zipper rope. Each
side of the zipper has teeth that only fit one
matching tooth: A pairs with T, and G pairs
with C.
• Cells divide to make new cells. Before dividing,
a cell must duplicate its instruction book
(DNA) so both new cells get a full copy.
• Smart idea (Watson & Crick): If each strand
carries the info to match the other, then
copying can be done by simply unzipping and
rebuilding the opposite side.
Analogy: Imagine a lined notebook page with
holes on the left. If you had only the “shadow” of
the holes, you could punch a new page that
matches perfectly. Each old strand is like a stencil
to punch a new partner.

2) Key term: “Semiconservative replication”

(Image 1 end)
 • “Semi” = half, “conserve” = keep.
• After copying, each new DNA has one old
strand and one newly made strand.
Analogy: You have a two-ply ticket. You keep one
original ply, and you print just the missing ply to
make a fresh two-ply ticket. Every final ticket = 1
old ply + 1 new ply.

3) The experimental proof (Image 2 heading and

Image 3 main)
This is the famous Meselson–Stahl experiment in
bacteria (E. coli).
• Step A: Grow bacteria in “heavy nitrogen”
(15N). Their DNA becomes heavier, like filling
a sponge with heavy water.
• Step B: Move them to normal “light nitrogen”
(14N) so any new DNA pieces are light.
• Step C: Spin DNA in a special salt solution
(CsCl). Heavy sinks lower, light stays higher,
hybrid sits in the middle. Think of washing
 pebbles in a bottle: big stones go to the
bottom, foam stays at the top, mixed stuff sits
halfway.
What did they see after each round of cell
division?
• After 1 division (~20 min): All DNA bands in
the middle — hybrid. Translation: each new
DNA = 1 heavy old strand + 1 light new strand.
• After 2 divisions (~40 min): Two bands — one
hybrid, one light.
• As divisions continue, the “light” band grows
while “hybrid” shrinks by half each
generation.
Quick mental math example for 80 minutes (~4
divisions):
• Gen1: 100% hybrid
• Gen2: 50% hybrid, 50% light
• Gen3: 25% hybrid, 75% light
• Gen4: 12.5% hybrid, 87.5% light
Analogy: Start with dark marbles. Each round,
every marble splits into two: one child keeps a
dark side glued to a new light side (hybrid), the
other that already had a light side can make a fully
light pair. Over time, light pairs dominate.

4) What machines do the copying? (Image 4:

“Machinery and Enzymes”)
Picture a road crew rebuilding a two-lane bridge
while traffic keeps moving. Each worker has a role:
• Helicase: The “zip opener.” It separates the
two strands — like unzipping a jacket.
• SSB proteins: Safety cones that hold lanes
apart so they don’t zip back.
• Topoisomerase: The anti-tangle crane that
removes twist-stress ahead of the unzip.
• Primase: Lays down a tiny starter piece (RNA
primer) — like placing the first brick so others
can follow.
 • DNA polymerase: The main builder. It adds
new nucleotides but can only build in one
direction (5'→3'). Also proofreads like a spell-
checker.
• DNA ligase: The glue gun that seals small gaps,
making one continuous strand.
• dNTPs: The bricks (A, T, G, C) that also bring
their own energy, like self-powered Lego
pieces.
Result: Two complete bridges (DNA double
helices), each with one original lane and one
newly built lane.

5) Why “leading” and “lagging”? (Image 5

diagram with 5’ and 3’ labels)
DNA polymerase can only add new pieces in the
5'→3' direction. Because the two original strands
run in opposite directions, copying proceeds
differently on each:
 • Leading strand: Built smoothly toward the
“replication fork” as it opens. Think of painting
a wall in one long roller stroke, moving
forward continuously.
• Lagging strand: Built in short segments away
from the fork (Okazaki fragments). It’s like
painting the same wall but having to step
back, paint a patch, step back again, paint
another patch, then later join all patches into
a clean coat with ligase.
Both meet the same rule (5'→3'), but geometry of
the fork forces one to be continuous and the
other discontinuous.

6) Where does copying start? “Origin of

replication” (Ori) (Image 4 text + Image 5 note)
• Ori is a fixed starting spot on DNA where the
zipper first opens.
• Bacteria usually have one Ori on their circular
chromosome — like opening a zip from one
 marked point and running around the circle in
both directions.
• Eukaryotes (plants, animals) have long linear
DNA with many Ori sites, so copying can start
at multiple places and finish on time — like
opening many zippers along a long sleeping
bag so the job finishes faster.

7) When does replication happen in higher

organisms? (Image 5 left text)
• In eukaryotes, DNA replication happens during
S-phase of the cell cycle.
Analogy: Think of the cell cycle as a school
day: S-phase is the “photocopy period” when
the library duplicates all notes before class
changes.
If cell division fails to coordinate with replication,
chromosome number can go wrong (polyploidy)
— like accidentally handing multiple photocopy
sets to one student and none to another.
8) Three models vs reality (quick compare)
• Conservative: Keep the entire old double-helix
untouched and make a fully new double-helix.
Not observed.
• Dispersive: Mix old and new in small pieces
throughout both strands. Not observed.
• Semiconservative: Each daughter has 1 old
strand + 1 new strand. This matches the
experiment and is the true mechanism.
Analogy trio:
• Conservative = “keep old book; print a brand-
new book separately.”
• Dispersive = “shred old book and mix pieces
with new print in both books.”
• Semiconservative = “bind one original page
with one freshly printed matching page.”

9) One-glance story flow

1. Unzip at Ori → fork forms.
 2. Helicase opens, SSB hold, topoisomerase
relaxes twists.
3. Primase lays primers.
4. DNA polymerase builds 5'→3'.
• Leading: smooth.
• Lagging: Okazaki fragments.
5. Replace primers, fill gaps, ligase seals.
6. Finish: Two DNAs, each = one old strand + one
new strand (semiconservative).
7. Proven by heavy/light nitrogen bands shifting
as generations pass.

10) Tiny practice Qs with quick answers

• Why is the first generation all “hybrid”?
Because every old strand pairs with a new
light strand, giving mixed density for every
molecule.
• After two generations, what fractions appear?
Half hybrid, half light. With each generation,
hybrid halves; light doubles.
• Why does the lagging strand need ligase?
It’s built in fragments; ligase seals the joints
into one continuous strand.
• What makes replication accurate?
Base-pair rules + DNA polymerase
proofreading.