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Page 1: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Lecture Presentations by

Nicole Tunbridge and

Kathleen Fitzpatrick

Chapter 16

Nucleic Acids

and Inheritance

© 2018 Pearson Education Ltd.

Page 2: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Life’s Operating Instructions

▪ In 1953, James Watson and Francis Crick

introduced an elegant double-helical model for the

structure of deoxyribonucleic acid, or DNA

▪ Hereditary information is encoded in DNA and

reproduced in all cells of the body

▪ This DNA program directs the development of

biochemical, anatomical, physiological, and

(to some extent) behavioral traits

© 2018 Pearson Education Ltd.

Page 3: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.1

© 2018 Pearson Education Ltd.

Page 4: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.1a

© 2018 Pearson Education Ltd.

Page 5: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ DNA is copied during DNA replication, and cells

can repair their DNA

© 2018 Pearson Education Ltd.

Page 6: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Concept 16.1: DNA is the genetic material

▪ Early in the 20th century, the identification of the

molecules of inheritance loomed as a major

challenge to biologists

© 2018 Pearson Education Ltd.

Page 7: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

The Search for the Genetic Material: Scientific

Inquiry

▪ When T. H. Morgan’s group showed that genes are

located on chromosomes, the two components of

chromosomes—DNA and protein—became

candidates for the genetic material

▪ The role of DNA in heredity was first discovered

by studying bacteria and the viruses that

infect them

© 2018 Pearson Education Ltd.

Page 8: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Evidence That DNA Can Transform Bacteria

▪ The discovery of the genetic role of DNA began with

research by Frederick Griffith in 1928

▪ Griffith worked with two strains of a bacterium, one

pathogenic and one harmless

© 2018 Pearson Education Ltd.

Page 9: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ When he mixed heat-killed remains of the

pathogenic strain with living cells of the harmless

strain, some living cells became pathogenic

▪ He called this phenomenon transformation, now

defined as a change in genotype and phenotype due

to assimilation of foreign DNA

© 2018 Pearson Education Ltd.

Page 10: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.2

Experiment

Living S cells(pathogeniccontrol)

Living R cells(nonpathogeniccontrol)

Heat-killed S cells(nonpathogeniccontrol)

Mixture of heat-killed S cells andliving R cells

Results

Mouse dies Mouse healthy Mouse healthy Mouse dies

Living S cells

© 2018 Pearson Education Ltd.

Page 11: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Later work by Oswald Avery, Maclyn McCarty, and

Colin MacLeod identified the transforming substance

as DNA

▪ Many biologists remained skeptical, mainly because

little was known about DNA

© 2018 Pearson Education Ltd.

Page 12: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Evidence That Viral DNA Can Program Cells

▪ More evidence for DNA as the genetic material

came from studies of viruses that infect bacteria

▪ Such viruses, called bacteriophages (or phages),

are widely used in molecular genetics research

▪ A virus is DNA (sometimes RNA) enclosed by a

protective coat, often simply protein

© 2018 Pearson Education Ltd.

Page 13: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.3

Phagehead

DNA

Tailsheath

Tail fiber

Geneticmaterial

Bacterialcell

100 n

m

© 2018 Pearson Education Ltd.

Page 14: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Animation: Phage T2 Reproductive Cycle

© 2018 Pearson Education Ltd.

Page 15: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ In 1952, Alfred Hershey and Martha Chase showed

that DNA is the genetic material of a phage known

as T2

▪ They designed an experiment showing that only one

of the two components of T2 (DNA or protein) enters

an E. coli cell during infection

▪ They concluded that the injected DNA of the phage

provides the genetic information

© 2018 Pearson Education Ltd.

Page 16: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.4

Labeled phagesinfect cells.

Agitation freesoutside phage partsfrom cells.

Centrifuged cellsform a pellet.

Measured theradioactivity inthe pellet andthe liquid.

Experiment

Emptyprotein shellRadioactive

protein

Radioactivity(phage protein)found in liquid

Phage

Bacterial cell

Batch 1: Radioactivesulfur (35S) in phageprotein

DNA

PhageDNA

Centrifuge

RadioactiveDNA

Pellet

Batch 2: Radioactivephosphorus (32P) inphage DNA

Centrifuge

Pellet

Radioactivity(phage DNA)found in pellet

1 2 3 4

© 2018 Pearson Education Ltd.

Page 17: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.4a

Experiment

Labeled phagesinfect cells.

Agitation freesoutside phageparts from cells.

EmptyproteinshellRadioactive

protein

Centrifugedcells forma pellet.

Measured theradioactivity inthe pellet andthe liquid.

Radioactivity(phage protein)found in liquid

Phage

Bacterial cell

Batch 1:Radioactive sulfur(35S) in phageprotein

DNA

PhageDNA

Centrifuge

Pellet

1 2 3 4

© 2018 Pearson Education Ltd.

Page 18: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.4b

Experiment

RadioactiveDNA

Batch 2:Radioactivephosphorus (32P)in phage DNA Centrifuge

PelletRadioactivity(phage DNA)found in pellet

© 2018 Pearson Education Ltd.

Page 19: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Animation: Hershey-Chase Experiment

© 2018 Pearson Education Ltd.

Page 20: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Additional Evidence That DNA Is the Genetic

Material

▪ DNA is a polymer of nucleotides, each consisting of

a nitrogenous base, a sugar, and a phosphate group

▪ The nitrogenous bases can be adenine (A), thymine

(T), guanine (G), or cytosine (C)

▪ In 1950, Erwin Chargaff reported that DNA

composition varies from one species to the next

▪ This evidence of diversity made DNA a more

credible candidate for the genetic material

© 2018 Pearson Education Ltd.

Page 21: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Two findings became known as Chargaff’s rules

▪ The base composition of DNA varies between species

▪ In any species the number of A and T bases is equal

and the number of G and C bases is equal

▪ The basis for these rules was not understood until

the discovery of the double helix

© 2018 Pearson Education Ltd.

Page 22: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.5

Thymine (T)

Guanine (G)

Cytosine (C)

Adenine (A)

Sugar–phosphatebackbone

Nitrogenous bases

5′ end

Phosphategroup

Sugar(deoxyribose)DNA

nucleotide Nitrogenous base

3′ end

© 2018 Pearson Education Ltd.

Page 23: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Animation: DNA and RNA Structure

© 2018 Pearson Education Ltd.

Page 24: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Building a Structural Model of DNA: Scientific

Inquiry

▪ After DNA was accepted as the genetic material, the

challenge was to determine how its structure

accounts for its role in heredity

▪ Maurice Wilkins and Rosalind Franklin were using a

technique called X-ray crystallography to study

molecular structure

▪ Franklin produced a picture of the DNA molecule

using this technique

© 2018 Pearson Education Ltd.

Page 25: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.6

© 2018 Pearson Education Ltd.

Page 26: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.6a

© 2018 Pearson Education Ltd.

Page 27: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.6b

© 2018 Pearson Education Ltd.

Page 28: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Franklin’s X-ray crystallographic images of DNA

enabled Watson to deduce that DNA was helical

▪ The X-ray images also enabled Watson to deduce

the width of the helix and the spacing of the

nitrogenous bases

▪ The pattern in the photo suggested that the DNA

molecule was made up of two strands, forming a

double helix

© 2018 Pearson Education Ltd.

Page 29: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7a

Structural Images

5′ end

Bases0.34 nmapart

3′ endDNA

nucleotide Sugar-phosphate

backbone

Sugar T A

One fullturn every10 basepairs(3.4 nm)

G C

C G

A T

3′ end

Diameter 2 nm 5′ end

© 2018 Pearson Education Ltd.

Page 30: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7aa

Bases0.34 nmapart

One fullturn every10 basepairs(3.4 nm)

Diameter 2 nm© 2018 Pearson Education Ltd.

Page 31: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7ab

5′ end 3′ end

DNAnucleotide

Sugar-phosphatebackbone

SugarT A

G C

C G

A T

3′ end

5′ end© 2018 Pearson Education Ltd.

Page 32: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7b

Simplified Images

5′

T A

G

C

C

G

A

T

C

G

C

A

G

T

A T

G

C

T

A

Nitrogenousbases

Sugar-phosphatebackbone

5′

T

G

C

A

C

G

T

3′ 5′

T

G

C

A

A

C

G

T

3′ 5′ 5′ 3′

3′

5′

A

5′ 3′ 5′ 3′ 5′ 3′

3′

3′3′

5′

© 2018 Pearson Education Ltd.

Page 33: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7ba

Simplified Images

5′

T

3′

A

G

C

C

G

A

T

C

G

G

C

T

A

Nitrogenousbases

Sugar-phosphatebackbone

C

A

G

T

A T

3′ 5′© 2018 Pearson Education Ltd.

Page 34: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.7bb

T

G

C

A

C

G

T

T

G

C

A

A

C

G

T

A

5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′

3′ 5′ 3′ 5′ 3′ 5′ 3′ 5′

© 2018 Pearson Education Ltd.

Page 35: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Animation: DNA Double Helix

© 2018 Pearson Education Ltd.

Page 36: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Video: Stick Model of DNA (Deoxyribonucleic Acid)

© 2018 Pearson Education Ltd.

Page 37: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Video: Surface Model of DNA (Deoxyribonucleic Acid)

© 2018 Pearson Education Ltd.

Page 38: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Watson and Crick built models of a double helix to

conform to the X-rays and chemistry of DNA

▪ Franklin had concluded that there were two outer

sugar-phosphate backbones, with the nitrogenous

bases paired in the molecule’s interior

▪ Watson built a model in which the backbones were

antiparallel (their subunits run in opposite

directions)

© 2018 Pearson Education Ltd.

Page 39: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ At first, Watson and Crick thought the bases paired

like with like (A with A, and so on), but such pairings

did not result in a uniform width

▪ Instead, pairing a purine (A or G) with a pyrimidine

(C or T) resulted in a uniform width consistent with

the X-ray data

© 2018 Pearson Education Ltd.

Page 40: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.UN02

Purine + purine: too wide

Pyrimidine + pyrimidine: too narrow

Purine + pyrimidine: widthconsistent with X-ray data

© 2018 Pearson Education Ltd.

Page 41: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Watson and Crick reasoned that the pairing was

more specific, dictated by the base structures

▪ They determined that adenine (A) paired only with

thymine (T), and guanine (G) paired only with

cytosine (C)

▪ The Watson-Crick model explains Chargaff’s rules:

in any organism the amount of A = T, and the

amount of G = C

© 2018 Pearson Education Ltd.

Page 42: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.8

Sugar

Sugar Sugar

Adenine (A) Thymine (T) Guanine (G) Cytosine (C)

Sugar

© 2018 Pearson Education Ltd.

Page 43: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Concept 16.2: Many proteins work together in

DNA replication and repair

▪ The relationship between structure and function is

manifest in the double helix

▪ Watson and Crick noted that the specific base

pairing suggested a possible copying mechanism for

genetic material

© 2018 Pearson Education Ltd.

Page 44: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

The Basic Principle: Base Pairing to a Template

Strand

▪ Since the two strands of DNA are complementary,

each strand acts as a template for building a new

strand in replication

▪ In DNA replication, the parent molecule unwinds,

and two new daughter strands are built based on

base-pairing rules

© 2018 Pearson Education Ltd.

Page 45: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.9_1

(a) Parentalmolecule

A

C

T

A

G

T

G

A

T

C

5′ 3′

3′ 5′

© 2018 Pearson Education Ltd.

Page 46: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.9_2

(a) Parentalmolecule

(b) Separation ofparental strandsinto templates

A

C

T

A

G

T

G

A

T

C

A

C

T

A

G

T

G

A

T

C

5′ 3′ 5′ 3′

3′ 5′ 3′ 5′

© 2018 Pearson Education Ltd.

Page 47: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.9_3

A

C

T

A

G

T

G

A

T

C

A

C

T

A

G

T

G

A

T

C

A

C

T

A

G

T

G

A

T

C

A

C

T

A

G

T

G

A

T

C

5′ 3′ 5′ 3′ 5′ 3′ 5′ 3′

3′

(a) Parentalmolecule

5′ 3′

(b) Separation ofparental strandsinto templates

5′ 3′ 5′ 3′ 5′

(c) Formation of newstrands complementaryto template strands

© 2018 Pearson Education Ltd.

Page 48: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Watson and Crick’s semiconservative model of

replication predicts that when a double helix

replicates, each daughter molecule will have one old

strand (derived or “conserved” from the parent

molecule) and one newly made strand

▪ Competing models were the conservative model (the

two parent strands rejoin) and the dispersive model

(each strand is a mix of old and new)

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Page 49: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.10

Parent cell

(a) Conservativemodel

Secondreplication

Firstreplication

(b) Semiconservativemodel

(c) Dispersivemodel

© 2018 Pearson Education Ltd.

Page 50: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Experiments by Matthew Meselson and Franklin

Stahl supported the semiconservative model

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Page 51: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.11

Predictions:

Conservativemodel

First replication Second replication

Semiconservativemodel

Dispersivemodel

Conclusion

Bacteria culturedin medium with15N(heavy isotope)

Bacteria transferredto medium with14N(lighter isotope)

DNA samplecentrifugedafter firstreplication

DNA samplecentrifugedafter secondreplication

Less dense

More dense

Experiment

Results

1 2

43

© 2018 Pearson Education Ltd.

Page 52: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.11a

Experiment

Bacteria culturedin medium with15N(heavy isotope)

Bacteria transferredto medium with14N(lighter isotope)

Results DNA samplecentrifugedafter firstreplication

DNA samplecentrifugedafter secondreplication

Less dense

More dense

1 2

3 4

© 2018 Pearson Education Ltd.

Page 53: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.11b

Conclusion

Predictions:

Conservativemodel

First replication Second replication

Semiconservativemodel

Dispersivemodel

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Page 54: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

DNA Replication: A Closer Look

▪ The copying of DNA is remarkable in its speed and

accuracy

▪ More than a dozen enzymes and other proteins

participate in DNA replication

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Page 55: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Getting Started

▪ Replication begins at particular sites called origins

of replication, where the two DNA strands are

separated, opening up a replication “bubble”

▪ A eukaryotic chromosome may have hundreds or

even thousands of origins of replication

▪ Replication proceeds in both directions from each

origin, until the entire molecule is copied

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Page 56: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.12

(a) Origin of replication in an E. coli cell

Origin ofreplication

Double-strandedDNAmolecule

Two daughterDNA molecules

Parental (template) strand

Daughter (new)strand

Replicationfork

Replicationbubble

(b) Origins of replication in a eukaryotic cell

Origin ofreplication

Parental(template) strand

Double-strandedDNA molecule

Daughter(new) strand

Bubble Replication fork

Two daughter DNA molecules

0.5

µm

0.2

5 µ

m

© 2018 Pearson Education Ltd.

Page 57: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.12a

(a) Origin of replication in an E. coli cell

Origin ofreplication

Double-strandedDNAmolecule

Two daughterDNA molecules

Parental (template) strand

Daughter (new)strand

Replicationfork

Replicationbubble

0.5

µm

© 2018 Pearson Education Ltd.

Page 58: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.12aa

0.5

µm

© 2018 Pearson Education Ltd.

Page 59: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.12b

(b) Origins of replication in a eukaryotic cell

Origin ofreplication

Parental(template) strand

Double-strandedDNA molecule

Daughter(new) strand

Bubble Replication fork

Two daughter DNA molecules

0.2

5 µ

m

© 2018 Pearson Education Ltd.

Page 60: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.12ba

0.2

5 µ

m© 2018 Pearson Education Ltd.

Page 61: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Animation: Origins of Replication

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Page 62: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ At the end of each replication bubble is a replication

fork, a Y-shaped region where new DNA strands are

elongating

▪ Helicases are enzymes that untwist the double helix

at the replication forks

▪ Single-strand binding proteins bind to and

stabilize single-stranded DNA

▪ Topoisomerase relieves the strain of twisting of the

double helix by breaking, swiveling, and rejoining

DNA strands

© 2018 Pearson Education Ltd.

Page 63: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Figure 16.13

TopoisomerasePrimase

3′5′

3′

RNAprimer

5′

3′

Helicase

Single-strand bindingproteins

Replicationfork

5′

© 2018 Pearson Education Ltd.

Page 64: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

Synthesizing a New DNA Strand

▪ DNA polymerases require a primer to which they can

add nucleotides

▪ The initial nucleotide strand is a short RNA primer

▪ This is synthesized by the enzyme primase

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Page 65: Chapter 16 Nucleic Acids and Inheritance - JU Medicine · 2020. 10. 8. · Chapter 16 Nucleic Acids and Inheritance. © 2018 Pearson Education Ltd. Life’s Operating Instructions

▪ Primase can start an RNA chain from scratch and

adds RNA nucleotides one at a time using the

parental DNA as a template

▪ The primer is short (5–10 nucleotides long), and the

3′ end serves as the starting point for the new DNA

strand

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▪ Enzymes called DNA polymerases catalyze the

synthesis of new DNA at a replication fork

▪ Most DNA polymerases require a primer and a DNA

template strand

▪ The rate of elongation is about 500 nucleotides per

second in bacteria and 50 per second in human cells

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▪ Each nucleotide that is added to a growing DNA

strand is a nucleoside triphosphate

▪ dATP supplies adenine to DNA and is similar to the

ATP of energy metabolism

▪ The difference is in their sugars: dATP has

deoxyribose while ATP has ribose

▪ As each monomer joins the DNA strand, via a

dehydration reaction, it loses two phosphate groups

as a molecule of pyrophosphate

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Figure 16.14

A

Base

C

G

T

G

C

A

C

New strand

5′

Phosphate

Sugar

OH

3′

Template strand

3′ 5′ 3′

5′

A T

Incomingnucleotide

OH

3′Pyro-

phosphate

DNApoly-

merase

C

G

G

C

A

C

5′

T

P

2

P i

P i© 2018 Pearson Education Ltd.

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Antiparallel Elongation

▪ The antiparallel structure of the double helix affects

replication

▪ DNA polymerases add nucleotides only to the free 3′

end of a growing strand; therefore, a new DNA

strand can elongate only in the 5′ to 3′ direction

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Figure 16.15

Overalldirections

of replication

OverviewLeadingstrand Origin of replication

Primer

Laggingstrand

Lagging strand

DNA pol III starts to synthesizethe leading strand.

Origin of replication

3′Single-strand binding

proteins5′

RNA primer5′ 3′ Sliding clamp3′

DNA pol IIIHelicase5′Parental DNA

3′

5′

Leadingstrand

5′

3′ 3′

5′

Continuous elongationin the 5′ to 3′ direction

2

1

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Figure 16.15a

Leadingstrand

Overview

Origin of replication Laggingstrand

Primer

LeadingstrandLagging strand Overall

directionsof replication

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Figure 16.15b

DNA pol III starts to synthesizethe leading strand.

Continuous elongationin the 5′ to 3′ direction

Single-strand bindingproteins

5′

3′

Helicase

Parental DNA

3′

Origin of replication

3′

5′

RNA primer

Sliding clamp

5′DNA pol III

3′

5′

5′

3′3′

5′

1

2

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▪ Along one template strand of DNA, the DNA

polymerase synthesizes a leading strand

continuously, moving toward the replication fork

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Animation: Leading Strand

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▪ To elongate the other new strand, called the lagging

strand, DNA polymerase must work in the direction

away from the replication fork

▪ The lagging strand is synthesized as a series of

segments called Okazaki fragments, which are

joined together by DNA ligase

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Figure 16.16

Leadingstrand

Overview

Origin of replication

Lagging strand

Laggingstrand

LeadingstrandOverall directions

of replication

RNA primerfor fragment 2

Okazakifragment 2

Templatestrand

RNA primerfor fragment 1

Okazakifragment 1

Overall direction of replication

Origin ofreplication

Primer forleadingstrand

Primase makesRNA primer.

DNA pol III

makes Okazakifragment 1.

Fragment 2is primed.

DNA ligase formsbonds betweenDNA fragments.

DNA pol Ireplaces RNAwith DNA.

DNA pol III

detaches. The laggingstrand iscomplete.

21

2

1

1

2

1

1

2

1

5′3′

3′

5′ 3′5′

5′

5′3′ 5′ 3′

5′

3′5′

3′3′

5′

3′5′

3′

3′

3′5′

5′

5′3′5′

3′

1

2

3

6

5

7

4

© 2018 Pearson Education Ltd.

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Figure 16.16a

Overview

Origin of replication

Leadingstrand

Lagging strand

21

Laggingstrand

Leadingstrand

Overall directionsof replication

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Figure 16.16b_1

Primase makesRNA primer. Origin of

replication

Templatestrand

3′

5′ 3′5′ 3′

5′

1 Primer forleadingstrand

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Figure 16.16b_2

Primase makesRNA primer. Origin of

replication

DNA pol IIImakes Okazakifragment 1.

Templatestrand

RNA primerfor fragment 1

3′

3′

5′ 3′5′ 3′

5′

5′1 3′ 5′ 3′

5′

1

2

Primer forleadingstrand

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Figure 16.16b_3

Origin ofreplication

DNA pol IIImakes Okazakifragment 1.

Templatestrand

RNA primerfor fragment 1

Okazakifragment 1

DNA pol IIIdetaches.

3′

3′

5′ 3′5′ 3′

5′

1 3′ 5′ 3′5′

3′

1 3′5′

5′

1

2

3

Primase makesRNA primer.

5′

Primer forleadingstrand

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Figure 16.16c_1

Fragment 2is primed.

RNA primer for fragment 2

Okazakifragment 23′

5′

2

1 3′5′

4

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Figure 16.16c_2

Fragment 2is primed.

DNA pol Ireplaces RNAwith DNA.

RNA primer for fragment 2

Okazakifragment 23′

5′

2

1

5′

1 3′5′

3′5′

3′

2

5

4

© 2018 Pearson Education Ltd.

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Figure 16.16c_3

DNA pol Ireplaces RNAwith DNA.

DNA ligase formsbonds betweenDNA fragments. The lagging

strand iscomplete.

RNA primer for fragment 2

Okazakifragment 2

Overall direction of replication

3′5′

2

1

5′

1

2

3′5′

3′5′

3′

2

3′5′

1 3′5′

6

7

5

4 Fragment 2is primed.

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Animation: Lagging Strand

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Animation: DNA Replication Overview

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Animation: DNA Replication Review

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Figure 16.17

Leading strandtemplate

Single-strandbinding proteins

Leading strand

Overview

Origin of replicationLaggingstrand

Leading strand

LeadingstrandLagging strand

Overall directionsof replication

Parental DNA

DNA pol III

Primer

Primase Lagging strand

DNA pol III

DNA pol I

Helicase

DNA ligase

Lagging strand template

5

4

3 2 1

5′

3′

5′

3′3′

5′ 3′

3′5′

5′

3′

5′

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Figure 16.17a

Overview

Origin of replication

Leading strandLaggingstrand

Lagging strand

Overall directionsof replication

Leadingstrand

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Figure 16.17b

Leading strandtemplate

Single-strandbinding proteins

Leading strand

DNA pol III

Primer

Parental DNA

Primase

Helicase

5′

3′

5′ 3′

5

3′

© 2018 Pearson Education Ltd.

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Figure 16.17c

Lagging strand

DNA pol IIIDNA pol I DNA ligase

Lagging strand template

4

3 2 1

5′3′5′

3′

5′

© 2018 Pearson Education Ltd.

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Table 16.1

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Table 16.1a

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Table 16.1b

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The DNA Replication Complex

▪ The proteins that participate in DNA replication form

a large complex, a “DNA replication machine”

▪ The DNA replication machine may be stationary

during the replication process

▪ Recent studies support a model in which DNA

polymerase molecules “reel in” parental DNA and

extrude newly made daughter DNA molecules

▪ The exact mechanism is not yet resolved

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Figure 16.18

Leading strand template

DNA pol III

Parental DNA

Connecting protein

DNA pol III

Laggingstrandtemplate

Helicase

Leading strand

Lagging strand

Overall direction of replication

3′5′

5′3′

5′

3′

5′

3′

5′ 3′

5′

3′

© 2018 Pearson Education Ltd.

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Proofreading and Repairing DNA

▪ DNA polymerases proofread newly made DNA,

replacing any incorrect nucleotides

▪ In mismatch repair of DNA, repair enzymes correct

errors in base pairing

▪ DNA can be damaged by exposure to harmful

chemical or physical agents such as cigarette smoke

and X-rays; it can also undergo spontaneous

changes

▪ In nucleotide excision repair, a nuclease cuts out

and replaces damaged stretches of DNA

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Figure 16.19_1

Nuclease

5′

3′

5′

3′

3′

5′

3′

5′

© 2018 Pearson Education Ltd.

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Figure 16.19_2

Nuclease

DNApolymerase

5′

3′

5′

3′

5′

3′

3′

5′

3′

5′

3′

5′

© 2018 Pearson Education Ltd.

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Figure 16.19_3

Nuclease

DNApolymerase

DNAligase

5′

3′

5′

3′

5′

3′

5′

3′

3′

5′

3′

5′

3′

5′

3′

5′© 2018 Pearson Education Ltd.

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Evolutionary Significance of Altered DNA

Nucleotides

▪ The error rate after proofreading and repair is low

but not zero

▪ Sequence changes may become permanent and

can be passed on to the next generation

▪ These changes (mutations) are the source of the

genetic variation upon which natural selection

operates and are ultimately responsible for the

appearance of new species

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Replicating the Ends of DNA Molecules

▪ Limitations of DNA polymerase create problems for

the linear DNA of eukaryotic chromosomes

▪ The usual replication machinery provides no way to

complete the 5′ ends, so repeated rounds of

replication produce shorter DNA molecules with

uneven ends

▪ This is not a problem for prokaryotes, most of which

have circular chromosomes

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Figure 16.20

Ends of parentalDNA strands

Last fragment

RNA primer

Leading strandLagging strand

Next-to-lastfragment

End oflagging strand

End ofparental strand

Removal of primers andreplacement with DNAwhere a 3′ end is available

Second roundof replication

New leading strand

New lagging strand

Further roundsof replication

Shorter and shorterdaughter molecules

5′

3′

5′

3′

5′

3′

5′

3′

5′

3′

© 2018 Pearson Education Ltd.

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Figure 16.20a

Ends of parentalDNA strands

Last fragment

RNA primer

Leading strandLagging strand

Next-to-lastfragment

End oflagging strand

End ofparental strand

Removal of primers andreplacement with DNAwhere a 3′ end is available

5′

3′

5′

3′

5′

3′© 2018 Pearson Education Ltd.

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Figure 16.20b

5′

3′

Second roundof replication

5′

New leading strand

New lagging strand

3′

Further roundsof replication

Shorter and shorterdaughter molecules

3′

5′

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▪ Eukaryotic chromosomal DNA molecules have

special nucleotide sequences at their ends called

telomeres

▪ Telomeres do not prevent the shortening of DNA

molecules, but they do postpone the erosion of

genes near the ends of DNA molecules

▪ It has been proposed that the shortening of

telomeres is connected to aging

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Figure 16.21

1 µm

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▪ If chromosomes of germ cells became shorter in

every cell cycle, essential genes would eventually be

missing from the gametes they produce

▪ An enzyme called telomerase catalyzes the

lengthening of telomeres in germ cells

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▪ The shortening of telomeres might protect cells from

cancerous growth by limiting the number of cell

divisions

▪ There is evidence of telomerase activity in cancer

cells, which may allow cancer cells to persist

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Concept 16.3: A chromosome consists of a

DNA molecule packed together with proteins

▪ The bacterial chromosome is a double-stranded,

circular DNA molecule associated with a small

amount of protein

▪ Eukaryotic chromosomes have linear DNA

molecules associated with a large amount

of protein

▪ In a bacterium, the DNA is “supercoiled” and found

in a region of the cell called the nucleoid

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▪ In the eukaryotic cell, DNA is precisely combined

with proteins in a complex called chromatin

▪ Chromosomes fit into the nucleus through an

elaborate, multilevel system of packing

▪ Proteins called histones are responsible for the first

level of packing in chromatin

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▪ Unfolded chromatin resembles beads on a string,

with each “bead” being a nucleosome, the basic

unit of DNA packaging

▪ They are composed of two each of the four basic

histone types, with DNA wrapped twice around the

core of the eight histones

▪ The N-termini (“tails”) of the histones protrude from

the nucleosome

▪ Nucleosomes, and especially their histone tails, are

involved in the regulation of gene expression

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Figure 16.22

Chromatid(700 nm)

DNAdouble helix(2 nm in diameter)

Nucleosome(10 nm in diameter)

30-nmfiber

Loopeddomain

Scaffold

300-nmfiber

Histone tailHistones

H1

Replicated chromosome(1,400 nm)

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Figure 16.22a

DNAdouble helix(2 nm in diameter)

Nucleosome(10 nm in diameter)

Histone tailH1

Histones

© 2018 Pearson Education Ltd.

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Figure 16.22aa

DNAdouble helix(2 nm in diameter)

© 2018 Pearson Education Ltd.

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Figure 16.22ab

Nucleosome(10 nm in diameter)

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Figure 16.22b

Chromatid(700 nm)

30-nmfiber

Loopeddomain

Scaffold

300-nmfiber

Replicated chromosome(1,400 nm)

© 2018 Pearson Education Ltd.

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Figure 16.22ba

30-nm fiber

© 2018 Pearson Education Ltd.

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Figure 16.22bb

Loopeddomain

Scaffold

© 2018 Pearson Education Ltd.

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Figure 16.22bc

Chromatid(700 nm)

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Animation: DNA Packing

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Video: Cartoon and Stick Model of a Nucleosomal Particle

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▪ Chromatin undergoes changes in packing during the

cell cycle

▪ At interphase, some chromatin seems to be

organized into a 10-nm fiber, but much is compacted

into a 30-nm fiber, through folding and looping

▪ Interphase chromosomes occupy specific restricted

regions in the nucleus, and the fibers of different

chromosomes do not become entangled

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Figure 16.23

5 µm

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Figure 16.23a

© 2018 Pearson Education Ltd.

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Figure 16.23b

© 2018 Pearson Education Ltd.

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Figure 16.23c

5 µm

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▪ Most chromatin is loosely packed in the nucleus

during interphase and condenses prior to mitosis

▪ Loosely packed chromatin is called euchromatin

▪ During interphase a few regions of chromatin

(centromeres and telomeres) are highly condensed

into heterochromatin

▪ Dense packing of the heterochromatin makes it

difficult for the cell to express genetic information

coded in these regions

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▪ Histones can undergo chemical modifications that

result in changes in chromatin condensation

▪ These changes can also have multiple effects on

gene expression

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Figure 16.UN01a

© 2018 Pearson Education Ltd.

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Figure 16.UN01b

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Figure 16.UN03

G

C

C

G

A T

A

Nitrogenousbases

Sugar-phosphatebackbone

C

A

T

C

G

G

T

G

C

Hydrogen bond

© 2018 Pearson Education Ltd.

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Figure 16.UN04

DNA pol III synthesizesleading strand continuously

ParentalDNA DNA pol III starts DNA

synthesis at 3′ end of primer,continues in 5′ → 3′ direction

Origin ofreplication

Helicase

Lagging strand synthesizedin short Okazaki fragments,later joined by DNA ligase

DNA pol I replaces the RNAprimer with DNA nucleotides

Primase synthesizesa short RNA primer

3′5′

5′3′

3′

5′1

2

4

3

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