Chapter 11

Nucleic Acid Structure,

DNA Replication and
Chromosome Structure

Key Concepts:
❑ Biochemical Identification of
the Genetic Material.
❑ Nucleic Acid Structure.
❑ An Overview of DNA
Replication.
❑ Molecular Mechanism of DNA
Replication.
❑ Molecular Structure of
Eukaryotic Chromosomes.
1
 Student Expected Learning Outcomes
1. Discuss properties of genetic material and experiments
that identified DNA as vector for genetic inheritance.
2. Outline structural features of DNA and interpret the work
of Franklin, Chargaff, Watson and Krick.
3. Discuss and interpret the work of Meselson and Stahl
regarding DNA replication.
4. Explain how DNA replicates and list the function of the
specialized enzymes involved in this process, and explain
how telomeric sequences are replicated.
5. Describe the structure of nucleosomes, which are the
building block of chromatin, and outline the various levels
of chromatin compaction that lead from interphasic DNA
to metaphase chromosomes.

2
 Biochemical Identification
of the Genetic Material

◼ What is the genetic material?

◼ Four criteria necessary for genetic material:
1. Information
2. Replication
3. Transmission
4. Variation

◼ Late 1800s – biochemical basis of heredity postulated.

◼ Researchers became convinced that chromosomes carry the
genetic information.
◼ 1920s to 1940s – scientists expected the protein portion of
chromosomes would turn out to be the genetic material.

3
 Griffith’s bacterial transformation
◼ Late 1920s – Frederick Griffith was working with
Streptococcus pneumoniae bacteria.
◼ Two strains of S. pneumoniae:
❑ Strains that secrete capsules look smooth (S)
and infections are fatal in mice
❑ Strains that do not secrete capsules look rough (R) and
infections are not fatal in mice

◼ The capsule shields the bacteria from the immune

system, so they survive in the blood.
Type R cells
Type S cells
1 Control: 2 Control:
are benign.
Injected living are virulent. Injected living
type S bacteria type R bacteria
into mouse. into mouse.

4
 Treatment Result Conclusion
◼ Smooth strains (S) with Control: Type S cells
capsule are fatal; rough
1
Injected living are virulent.
type S bacteria

strains (R) without

into mouse.

capsule are not.

2 Control: Type R cells

◼ If mice are injected Injected living

type R bacteria
are benign.

with heat-killed type S,

into mouse.

they survive (because

bacteria are dead). 3 Control:
Injected heat-
Heat-killed
type S cells
killed type S are benign.

However, mixing live R

bacteria
◼ into mouse.

with heat-killed S kills

the mouse. Living type
Injected living
Blood is found to contain
4 R cells have
❑ type R and
heat-killed been

living type S bacteria. type S bacteria transformed

into mouse. into virulent
type S cells

Known as
by a
❑ substance

transformation.
from the
Virulent type S heat-killed
strain in dead type S cells.
mouse’s blood
5
◼ How is this possible?
◼ Genetic material had been transferred
from the heat-killed type S bacteria to the
living type R bacteria.
◼ This gave them the capsule-secreting trait
and was passed on to their offspring.
◼ What was the biochemical basis of this
transforming principle? At the time there was
no way to know.

6
 Nucleic Acid Structure

Levels of DNA Structure: Nucleotides

1. Nucleotides – the building blocks

of DNA and RNA.
Single strand

2. Strand – a linear polymer strand

of DNA or RNA.
Double helix
3. Double helix – the two strands of
DNA.
4. Chromosomes – DNA associated
with an array of different DNA associates with
proteins to form a
proteins into a complex structure. chromosome.

5. Genome – the complete

complement of genetic material in
an organism.
7
 DNA
◼ Formed from nucleotides (A, G, C, T),

◼ Nucleotides composed of
three components:
❑ Phosphate group
Base
❑ Pentose sugar
◼ Deoxyribose
Phosphate
◼ DNA = Deoxyribonucleic Acid

❑ Nitrogenous base Deoxyribose

◼ Purines – Adenine (A), Guanine (G)

◼ Pyrimidines – Cytosine (C), Thymine (T)
8
DNA nucleotides
Purines Pyrimidines
(double ring) (single ring)

Base NH2 O
O– CH3 H
N N
O P O CH2 N
O H
O– N H O
H H H N N
H
Phosphate H H
OH H Adenine (A) Thymine (T)

Deoxyribose O NH2
N H H
N N
H
N N NH2 H N O
H H
Guanine (G) Cytosine (C)
(a) DNA nucleotide
9
RNA
◼ Formed from nucleotides (A, G, C, U)

◼ Nucleotides composed of H
three components:
❑ Phosphate group
Base
❑ Pentose sugar
◼ Ribose
Phosphate
◼ RNA = Ribonucleic Acid
OH
Ribose
❑ Nitrogenous base
◼ Purines – Adenine (A), Guanine (G)
◼ Pyrimidines – Cytosine (C), Uracil (U)
10
RNA nucleotides
Purines Pyrimidines
(double ring) (single ring)
Base NH2
O–
N H H
O P O CH2 N
O H
O– N H
H H N
H H
H
Phosphate H
OH OH Adenine (A) Uracil (U)
Ribose O NH2
N H H
N N
H
N NH2 H O
N N
H H
Guanine (G) Cytosine (C)
(b) RNA nucleotide
11
Nucleotide numbering system
◼ Sugar carbons are 1’ to 5’ (clockwise).
◼ Base attached to 1’ carbon on sugar.
◼ Phosphate attached to 5’ carbon on sugar.
O
4
CH3 5 H
N
3 Thymine
6
H 2 O
O– 1
N

O P O CH2
5′ O
O– 1′
4′ H H
Phosphate H H
3′ 2′
OH H
Deoxyribose
12
Strands
Backbone Bases
O

Nucleotides are
H
CH3 N

◼ H O
Thymine (T)

covalently bonded.
O– N

5′ O P O CH2
5′ O
O– 1′
4′
H H H H

Phosphodiester bond
2′

◼
3′ NH2
H
N
N

– phosphate group links

O H
Adenine (A)
N H
O P O CH2 N
5′ O

two sugars.
O– 1′
4′
H H NH2
H H
2′ H
3′ N
H
Cytosine (C)

Backbone – formed from

H O

◼ Phosphodiester
O N

linkage
O P O CH2

phosphates and sugars.

5′ O
O–
4′ 1′
H
H H
H Guanine (G)
2′ O
3′

Bases project away

H N H
N

◼
H
O
N NH2
N
Single
from backbone.
O P O CH2
5′ O

nucleotide O– 4′
H H
1′

Phosphate
H H
2′
3′

Written 5’ to 3’
OH H

◼ Sugar (deoxyribose)

3′
◼ ex: 5’ –TACG – 3’
13
 Solving the structure of DNA
◼ 1953, James Watson and Francis Crick, proposed the structure of
the DNA double helix.

◼ Watson and Crick used Linus Pauling’s method

of working out protein structures using simple
ball-and-stick models.

◼ Rosalind Franklin’s
X-ray diffraction results
were crucial evidence,
suggesting a helical structure
with uniform diameter .

14
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X-rays diffracted by DNA

onto photographic plate
Pattern represents the
atomic array in wet fibers

Wet DNA fibers

X-ray beam

15
Base-pairing

◼ Erwin Chargaff
analyzed base
composition of DNA
from many different
species.

◼ Results consistently
showed:
amount of A = amount of T

amount of C = amount of G

16
Watson and Crick
◼ Put together these pieces of information.
◼ Found ball-and-stick model consistent with
data:
❑ Double-stranded helix
❑ Base-pairing: A with T and G with C

◼ James Watson, Francis Crick, and Maurice

Wilkins awarded Nobel Prize in 1962.
◼ Rosalind Franklin had died and the Nobel Prize is
not awarded posthumously.
17
Features of DNA (a) Double helix 5′ end

Bases
Double stranded
3′ end
◼

◼ Antiparallel strands Hydrogen bond

◼ Right-handed helix Sugar-phosphate

backbone

◼ Sugar-phosphate
backbone Complete turn
of the helix
◼ Bases on the inside 3.4 nm

◼ Stabilized by H-bonding

◼ Specific base-pairing One nucleotide

0.34 nm

◼ ~10 nts per helical turn

5′ end
3′ end

2 nm
18
(b) Base pairing
Key Features:
• Two strands of DNA form a double helix.
• The bases in opposite strands hydrogen-bond according to the AT/GC rule.
• The 2 strands are antiparallel.
• There are ~10 nucleotides in each strand per complete turn of the helix.

5′ end 3′ end
HO
H

Adenine
H H H H
O–
O
N N CH2 O P O
H
H O
N
N
O H
O– N
5′ phosphate O P O CH2
O N O
H H H
O–
H
H H H
H CH3
Guanine H H H
H
O–
H O
H N
Thymine N N CH2 O P O
H
H O
N
O H N
O N
H O
O P O CH2 N N
O H
O – H
H H H H H H Guanine H H H H
O–
H Cytosine H O
N CH2 O P O
H N N
H O–
N
O H N
O N
H O
O P O CH2 N N
O
O– H
H H H
H H H

Cytosine Hydrogen
3′ hydroxyl OH H
bond
3′ end 5′ end
◼ Chargaff’s rule
❑A pairs with T
❑ G pairs with C
❑ Keeps width consistent

◼ Complementary DNA strands

❑ 5’ – GCGGATTTGG – 3’ G+A = T+C 10 = 10
❑ 3’ – CGCCTAAACC – 5’

◼ Antiparallel strands
❑ One strand 5’ to 3’
❑ Other stand 3’ to 5’

20
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◼ Grooves are revealed

in the space-filling
model.
Major groove

Major groove
Minor groove
◼
❑ Proteins
bind to affect
gene expression Major groove

◼ Minor groove
❑ Narrower Minor groove

21
 An Overview of DNA Replication

◼ Late 1950s – three different models were

proposed for DNA replication.
❑ Semiconservative Model
❑ Conservative Model
❑ Dispersive Model

◼ Newly-made strands are “daughter strands”.

◼ Original strands are “parental strands”.

22
Semiconservative Mechanism
Original First round Second round
double helix of replication of replication

Parental strand
Daughter strand

(a) Semiconservative mechanism. DNA replication produces

DNA molecules with 1 parental strand and 1 newly made
daughter strand.
23
Conservative Mechanism
Original First round Second round
double helix of replication of replication

(b) Conservative mechanism. DNA replication produces 1 double

helix with both parental strands and the other with 2 new
daughter strands.

24
Dispersive Mechanism
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Original First round Second round

double helix of replication of replication

(c) Dispersive mechanism. DNA replication produces DNA

strands in which segments of new DNA are interspersed
with the parental DNA.
25
Meselson and Stahl experiment
◼ In 1958, Matthew Meselson and Franklin Stahl
devised an experiment to differentiate among the
three proposed DNA replication mechanisms.
◼ Nitrogen comes in a common light form (14N) and
a rare heavy form (15N).
◼ Grew E. coli in medium with 15N to label, then
switched to medium with 14N, collecting samples
after each generation.
◼ Original parental strands would be 15N while newly
made strands would be 14N.
◼ Conclusion: Semiconservative DNA replication.
26
 5 THE DATA
1 Grow bacteria in 15N 2 Transfer to 14N media and
media. continue growth for <1,
1.0, 2.0, or 3 generations. Approximate generations after transfer to 14N medium.
15Nmedium 14N medium
< 1.0 1.0 2.0 3.0
(heavy) (light)

Light

Half-heavy
Heavy

Isolate DNA after each generation. Transfer

3 DNA to CsCl gradient, and centrifuge.

DNA

CsCl gradient

Centrifuge

4 Observe DNA under UV light.

27
Semiconservative replication
5′ 3′

The two parental C G 5′ 3′

◼ C G

strands separate
C G AT
C G
T A

and serve as
AT G C
C G G C
T A

template strands.
CG AT
Replication
A T C G
fork
A T
GC

New nucleotides
A T GC
◼ C G
3′
T A
5′

must obey the

A T
G C
C 5′ 3′ 5′ 3′
AT/GC rule.
G
T A T A CG C G
A T A T
CG C G
AT AT T A T A

End result: two new T A T A G C G C

◼ CG CG GC
T A
GC
T A

double helices with

T A Incoming T A
nucleotides A T A T
CG C G

same base sequence

GC C AT AT
GC GC
CG G GC GC

as original.
3′ T A A 5′ T A T A
Original Newly Original 3′ 5′ 3′ 5′
(template) synthesized (template)
(b) The products of replication
strand daughter strand strand
(a) The mechanism of DNA replication
28
 Molecular Mechanism
of DNA Replication

◼ Origin of replication provides an opening called a

replication bubble that forms two replication forks.
◼ DNA replication proceeds outward from forks.
◼ Bacteria have single origin of replication.
◼ Eukaryotes have multiple origins of replication.

29
 A) Bidirectional replication B) Single origin of replication in bacteria C) Multiple origins of replication
in eukaryotes

Origin of Origin of Origin of

replication replication replication
Circular
bacterial
chromosome Site where
1 DNA strands unwind. DNA replication 1 DNA strands unwind,
1 ends and DNA replication
DNA strands unwind,
begins at multiple
and DNA replication
origins of replication.
begins.

2 DNA replication begins outward

from two replication forks.

2 DNA replication
is completed.
Replication
forks
3 DNA replication 2 DNA replication
continues in both is completed.
directions.

Replication
fork

Kinetochore proteins
at the centromere
Replication
fork

30
◼ DNA helicase
❑ Binds to DNA and travels 5’ to 3’ using ATP
to separate strand and move fork forward.

◼ DNA topoisomerase
❑ Relieves additional coiling ahead of
replication fork.

◼ Single-strand binding proteins

❑ Keep parental strands open to act as
templates.

31
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Single-strand binding proteins

DNA topoisomerase coat the DNA strands to prevent
travels slightly ahead them from re-forming a double helix.
of the replication fork
and alleviates coiling
caused by the action 3′
of helicase.

5′
DNA helicase travels
3′ along one DNA strand
in the 5′ to 3′ direction
and separates the DNA
strands.

Direction of replication fork

5′
32
◼ DNA polymerase
❑ Covalently links nucleotides.
❑ Deoxynucleoside triphosphates.

DNA polymerase
catalytic site 5′

3′
Incoming
deoxynucleoside
triphosphates
(a) Action of DNA polymerase
33
 Deoxynucleoside triphosphates
❑ Free nucleotides with three phosphate groups.
❑ Breaking covalent bond to release pyrophosphate (two
phosphates) provides energy to connect nucleotides.

A 3′ end
T
G 3′ end
C Template H HO
H HO
G strand
HH H H H H H
C H
O–
O–
O O
N
5′ end H N N CH2 O P O H N CH2 O P O
5′ end A
N
A H O
N
H O
N N
O H O H
O– H O– H N H
H N
O P O CH2 O P O CH2
O N T O H H H H H O N T O H H
H H
H
O– H O– O– H O–
H HH H H O
H H CH3 O H H H CH3 N
H N N N CH2 O P O H N N CH2 O P O
H G
H
N
G H O
N
H O
H N O H N
O O
O N H N H
O O
O P O CH2
O P O CH2
O N C N H
H H O N C N H
H H
O– HH O– H H
H H O– H H H H O–
H H HH
H H O H H H H O
N CH2 O P O H N N N CH2 O P O
H N N
OH H H
G H O–
N
G H O–
N
3′ end H N O H N
5′ end
O
5′ end O N
O
O P O CH2
O N C N H
C O–
New phosphoester H H H
H H H H O O
bond
OH H + –O P O P O–
–O O–
3′ end Pyrophosphate
An incoming nucleotide
(a deoxynucleoside triphosphate) +
(b) Chemistry of DNA replication Phosphate
Features of DNA polymerase

1. DNA polymerase cannot begin synthesis

on a bare template strand.
❑ Requires a primer to get started
❑ DNA primase makes the primer from RNA
❑ The RNA primer is removed and replaced
with DNA later

2. DNA polymerase only works 5’ to 3’

35
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DNA polymerase is able to DNA polymerase can link

covalently link nucleotides nucleotides only in the
together from a primer, which 5′ to 3′ direction.
is made by DNA primase.
3’

5’

5’ 5′ 3′

3’ RNA
primer 3′ 5′
5’
3’
3’

(a) Need for a primer 5’ (b) 5′ to 3′ direction of

DNA synthesis

36
◼ Leading strand:
❑ DNA synthesized as one long molecule
❑ DNA primase makes a single RNA primer
❑ DNA polymerase adds nucleotides in a 5’ to 3’ direction
as it slides forward

◼ Lagging strand:
❑ DNA synthesized 5’ to 3’ but as Okazaki fragments
❑ Okazaki fragments consist of RNA primers plus DNA

◼ In both strands:
❑ RNA primers are removed by DNA polymerase and
replaced with DNA
❑ DNA ligase joins adjacent DNA fragments

37
 1 DNA strands separate at an
origin of replication, creating
2 replication forks.

Replication
forks

2 Primers are needed to initiate

DNA synthesis. The synthesis
of the leading strand begins in
the direction of the replication
fork. In the lagging strand, the Leading RNA primer
first Okazaki fragment is made strand
in the opposite direction. 3′

5′
5′
3′
Direction of
replication fork
3′
5′ 1
Primer
3′
3 The leading strand elongates, First Okazaki fragment 5′
and a second Okazaki fragment of the lagging strand
is made. 3′
5′

5′ 3′
Second First
Okazaki Okazaki
3′ fragment fragment
5′ 2
1
3′
38
5′
 4 The leading strand continues
to elongate. A third Okazaki
fragment is made, and the first
and second are connected
together.

3′

5′
3′
3′ Third First and second Okazaki
5′ Okazaki fragments have been
fragment connected to each other.
5′
3′
5′

39
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Origin of replication

Leading Lagging
strand strand
5′ 3′
Replication Replication
fork fork
3′ 5′
Lagging Leading
strand strand

(b) Replication from an origin

40
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DNA
1 DNA primase makes RNA primers to begin primase 3′ 3 DNA polymerase III continues to elongate
the replication process. 5′ the leading strand. In the lagging strand,
DNA polymerase III synthesizes DNA
from the second primer. DNA polymerase
I removes the first primer and replaces it
with DNA.

5′ RNA
primer 3′
3′
5′
5′

5′ 3′
Missing
Second covalent bond
primer
2 DNA polymerase III makes DNA from the 3′
Third
RNA primers. DNA primase hops back to
primer
the opening of the fork and makes a second 5′
RNA primer for the lagging strand. Clamp
protein
3′
Direction of replication fork 4 In the lagging strand, DNA ligase forms a DNA
5′ polymerase I
DNA covalent bond between the first and second
polymerase III Okazaki fragments. A third Okazaki
Leading fragment is made. The leading strand
strand
5′ continues to elongate.
Second DNA
3′ primer polymerase III
3′
DNA
primase 3′
First 5′
5′ 5′
RNA primer
3′ DNA ligase
Lagging strand
(Okazaki
fragment)
3′
Third
5′
primer
DNA replication is very accurate

◼ Three mechanisms for accuracy:

1. Hydrogen bonding between A and T,
and between G and C is more stable than
mismatched combinations

2. Active site of DNA polymerase is unlikely to

form bonds if pairs mismatched

3. DNA polymerase can proofread to remove

mismatched pairs
◼ DNA polymerase backs up and digests linkages
◼ Other DNA repair enzymes as well

42
 DNA Polymerases Are a Family of
Enzymes With Specialized Functions

◼ Important issues for DNA polymerase are speed,

fidelity, and completeness.

◼ Nearly all living species have more than one type of

DNA polymerase.

◼ Genomes of most species have several DNA

polymerase genes due to gene duplication.

◼ Independent genetic changes produce enzymes with

specialized functions.
◼ E. coli has 5 DNA polymerases:
❑ DNA polymerase III – multiple subunits,
responsible for majority of replication.
❑ DNA polymerase I – a single subunit, rapidly
removes RNA primers and fills in DNA.
❑ DNA polymerases II, IV and V – DNA repair
and can replicate damaged DNA.
◼ DNA polymerases I and III stall at DNA damage
◼ DNA polymerases II, IV and V don’t stall but go
slower and make sure replication is complete
◼ Humans have 12 or more DNA polymerases:
❑ Designated with Greek letters.
❑ DNA polymerase α – its own built in primase subunit.
❑ DNA polymerase δ (lagging strand) and ε (leading
strand) – extend DNA at a faster rate.
❑ DNA polymerase γ – replicates mitochondrial DNA.
❑ When DNA polymerases α, δ or ε encounter
abnormalities they may be unable to replicate.
❑ Lesion-replicating
polymerases may be able to
synthesize complementary strands to the damaged
area.
Telomeres

◼ Series of short nucleotide sequences (5’-

GGGTTA-3’)n repeated at the ends of
chromosomes in eukaryotes.
◼ Specialized form of DNA replication only in
eukaryotes in the telomeres.
◼ Telomere at 3’ end does not have a
complementary strand and is called a 3’
overhang.

47
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Telomere repeat sequences

3′

GGG T T AGGG T T AGGG T T AGGG T T A GGG T T A

CCCAATCCCAATCCCAAT
3′ overhang
5′

48
◼ DNA polymerase cannot copy the tip of
the strand with a 3’ end.
❑ No place for upstream primer to be made

◼ If this replication problem were not

solved, linear chromosomes would become
progressively shorter.
◼ Telomerase enzyme attaches many copies
of DNA repeat sequence to the ends of
chromosomes.

49
◼ Shortening of telomeres is correlated
with cellular senescence.
◼ Telomerase function is reduced as an
organism ages.
◼ 99% of all types of human cancers have
high levels of telomerase.

50
 Mechanism of Telomere Replication
Telomere Eukaryotic Telomere
chromosome
5′ 3′
3 Telomerase moves 6 nucleotides
3′ 5′ to the right and begins to make
another repeat.
1 Telomerase binds to a
DNA repeat sequence.
T A G G G T T A G G G T T A GG G T T A G G G T T AG GG T
Repeat sequence A T C C CA A T A A U C C C AAU
5′ 3′

T A G G G T T AG G G T T AG G G T T A
AT C CCAA T A A U C C C AA U

3′ 5′ RNA in
telomerase

Telomerase

4 Primase makes an RNA primer near the end of

2 Telomerase synthesizes
the telomere, and DNA polymerase III synthesizes
a 6-nucleotide repeat
a complementary strand in the 5′ to 3′ direction.
sequence.
The RNA primer is eventually removed.

5′ 3′

T A GG G T T A GG G T T A GG GT T A GG G T T A GG G T T A
T A G G G T T A G G G T T A G G G T T A GG G T A T C C C A A T C C C A AT C C CA A U C C C A A U C C C
AT CCCAA T A A U C C C AAU
3′ 5′
RNA primer that is
eventually removed
 Molecular Structure of
Eukaryotic Chromosomes

◼ Typical eukaryotic chromosome may be hundreds

of millions of base pairs long.
❑ Length of human DNA would be 2 meters
❑ But must fit in the cell nucleus  10µm

◼ Chromosome
❑ Discrete unit of genetic material

◼ Chromosomes composed of chromatin

❑ DNA-protein complex

53
Three levels of DNA compaction

1. DNA wrapping
❑ DNA wrapped around histones to form
nucleosomes.
❑ Shortens length of DNA molecule 7-fold.

2. 30-nm fiber
❑ Currentmodel suggests asymmetric, 3D zigzag of
nucleosomes.
❑ Shortens length another 7-fold.

54
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Nucleosome:
8 histone proteins +
146 or 147 nucleotide
base pairs of DNA

DNA
H4 H3
Amino
(a) Micrograph of a 30-nm fiber
terminal
H4 tail of
Linker
H2A region histone
H2B protein
H2B

30 nm

H1
11 nm

(b) Three-dimensional zigzag model

a: Photo courtesy of Dr. Barbara HamkaloZ

55
 Radial loop domains
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3. Protein fiber inside the nucleus

❑ Interaction between 30-nm fiber

30-nm fibers and

nuclear matrix.
❑ Each chromosome
located in discrete
territory. Radial loop
domain

◼ Level of compaction is
not uniform.
❑ Heterochromatin Protein that attaches the base
of a DNA loop to a protein fiber
❑ Euchromatin

56
Cell division

◼ When cells prepare to divide, chromosomes

become even more compacted.
❑ Euchromatin not as compact

❑ Heterochromatin much more compact

◼ Metaphase chromosomes highly compacted

57
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DNA double helix

2 nm

(a) DNA double helix

1 Wrapping of DNA around
11 nm histone proteins

Histones

Nucleosome

(b) Nucleosomes (“beads on a string”) 2 Formation of a 3-dimensional

Histone H1 zigzag structure via histone
H1 and other DNA-binding
proteins

(c) 30-nm fiber 30 nm

a: © Dr. Gopal Murti/Visuals Unlimited; b: © Ada L. Olins and Donald E. Olins/Biological Photo Service; c: Courtesy Dr. Jerome B. Rattner,
Cell Biology and Anatomy, University of Calgary

58
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

300 nm 3 Anchoring of radial loop

domains to the nuclear matrix

(d) Radial loop domains

4 Further compaction of radial

loops to form heterochromatin

700 nm

(e) Heterochromatin
5 Metaphase chromosome with
2 copies of the DNA

1,400 nm

(f) Metaphase chromosome

d: Courtesy of Paulson, J.R. & Laemmli, U.K. James R. Paulson, U.K. Laemmli, “The structure of histonedepleted
metaphase chromosomes,” Cell, 12:817–28, Copyright Elsevier 1977; e-f: © Peter Engelhardt/
Department of Virology, Haartman Institute

59
 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

DNA double helix

2 nm

(a) DNA double helix

1 Wrapping of DNA around
11 nm histone proteins

Histones
Nucleosome
(b) Nucleosomes (“beads on a string”) 2 Formation of a 3-dimensional
Histone H1 zigzag structure via histone
H1 and other DNA-binding
proteins

(c) 30-nm fiber

30 nm

3 Anchoring of radial loop

300 nm
domains to the nuclear matrix

(d) Radial loop domains

4 Further compaction of radial

loops to form heterochromatin

700 nm

(e) Heterochromatin
5 Metaphase chromosome with
2 copies of the DNA

1,400 nm

(f) Metaphase chromosome

a: © Dr. Gopal Murti/Visuals Unlimited; b: © Ada L. Olins and Donald E. Olins/Biological Photo Service; c: Courtesy Dr. Jerome B. Rattner, Cell Biology and 60
Anatomy, University of Calgary; d: Courtesy of Paulson, J.R. & Laemmli, U.K. James R. Paulson, U.K. Laemmli, “The structure of histonedepleted
metaphase chromosomes,” Cell, 12:817–28, Copyright Elsevier 1977; e-f: © Peter Engelhardt/Department of Virology, Haartman Institute
 Student Expected Learning Outcomes
1. Discuss properties of genetic material and experiments
that identified DNA as vector for genetic inheritance.
2. Outline structural features of DNA and interpret the work
of Franklin, Chargaff, Watson and Krick.
3. Discuss and interpret the work of Meselson and Stahl
regarding DNA replication.
4. Explain how DNA replicates and list the function of the
specialized enzymes involved in this process, and explain
how telomeric sequences are replicated.
5. Describe the structure of nucleosomes, which are the
building block of chromatin, and outline the various levels
of chromatin compaction that lead from interphasic DNA
to metaphase chromosomes.

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