BIOL 2533 Genetics

DNA Structure and Replication

Chapter7
 Modern Genetics Has Three Major Branches

Transmission genetics (Mendelian genetics) is

the study of the transmission of traits in
successive generations

Evolutionary genetics studies the origins of and

genetic relationships between organisms, and
evolution of genes and genomes

Molecular genetics studies inheritance and

variation of nucleic acids and proteins
2
 1.2 The Structure of DNA Suggests a
Mechanism for Replication
Identification of DNA as the hereditary material was
the foundation of new molecular-focused
approaches in biological research

The molecular structure of DNA was key to

understanding:
– How DNA could carry genetic information
– How the molecule replicated

3
 The DNA Double Helix

Watson and Crick published the structure of

DNA in 1953

The structure was described as a double helix

with sugar phosphate backbones on the
outsides and nucleotide bases arrayed in
complementary pairs toward the center

Other researchers made significant

contributions to understanding DNA structure
4
 Rosalind Franklin

Rosalind Franklin, a biophysicist, used x-ray

diffraction to examine the crystal structure of DNA

X-rays that pass through the crystalized structure

are diffracted, creating a pattern collected on x-ray
film

Watson and Crick used Franklin’s x-ray diffraction

data to deduce that DNA structure was a double
helix

5
6
 Erwin Chargaff

Chargaff discovered that for most organisms the

percentage of adenine and thymine are equal,
and the percentage of guanine and cytosine are
equal

This is known as Chargaff’s rule

Watson and Crick used Chargaff’s rule to

formulate the hypothesis that nucleotides are
arranged as complementary base pairs (A with T
and C with G)

7
8
9
 DNA Nucleotides

DNA nucleotides are composed of a deoxyribose (5-

carbon) sugar, a phosphate group, and one of four
nitrogenous bases designated:
– Adenine (A)
– Guanine (G)
– Thymine (T)
– Cytosine (C)
Nucleotides are linked together by a phosphodiester
bond between the 5¢ phosphate group of one
nucleotide and the 3¢ hydroxyl of another
10
11
 Complementary Base Pairing

Complementary base pairing occurs between an A

on one strand and a T on the other, or a G on one
strand and a C on the other

Hydrogen bonds form between the complementary

base pairs

The 5¢ and 3¢ designations of the phosphate and

hydroxyl at the ends of the DNA strands establish
polarity; the two strands are antiparallel

12
 DNA Replication

Each single strand of DNA contains the information

needed to generate its complementary strand

Meselson and Stahl demonstrated that DNA

replication was semiconservative about 5 years
after DNA structure was elucidated

Semiconservative replication creates two new

duplexes, each composed of one parental (original)
strand and one newly made daughter strand

13
14
 1.3 Transcription and Translation Express Genes
The central dogma of biology describes the flow of
hereditary information; the original was proposed
by Francis Crick

15
 Types of RNA

Several types of RNA are produced in a cell;

messenger RNA (mRNA) is the only type that is
translated

Ribosomal RNA (rRNA) forms part of the

ribosomes

Transfer RNA (tRNA) carries amino acids to

ribosomes, to be assembled into proteins
16
Additional Features of an Updated Central Dogma

Reverse transcription uses reverse transcriptase

and an RNA template (from
RNA-containing viruses) to produce complementary
DNA
Micro-RNAs are small RNA molecules with roles in
regulation of gene expression in plants and animals

17
 Transcription

Transcription uses one strand of DNA to direct

synthesis of a single-stranded RNA transcript

The DNA strand from which the RNA is

synthesized is called the template strand

The complementary partner of the template

strand is called the coding strand

18
19
 Features of RNA

RNA consists of ribose, a phosphate group, and

one of four nucleotide bases; three of these – A,
C, and G – are the same as DNA

Uracil replaces thymine in RNA; U pairs with A in

RNA:RNA complementary base pairing

RNA polymerase is the enzyme that synthesizes

RNA transcripts

20
 Regulation of Transcription

Promoters help regulate the initiation of

transcription, which begins near the promoter
site at the start of transcription

Transcription ends at the termination sequence

Eukaryotic genes have exons, with coding

information, and introns that are removed from
the transcript prior to translation
21
22
 Translation

Translation converts the genetic message carried

by mRNA into a sequence of amino acids joined
together by covalent peptide bonds at the
ribosome

The resulting polypeptide, upon folding, makes

up all or part of a protein

Each amino acid is specified by a codon, three

consecutive nucleotides on the mRNA
23
 The Beginning of Translation

Translation begins when mRNA attaches to the

ribosome in a manner that places the start
codon in the correct position

The start codon is usually AUG; from here,

ribosomes move in the 5¢ to 3¢ direction along
the mRNA to assemble the specified amino acid
chain

24
25
26
27
 The Process of Translation

Amino acids are transported to ribosomes by

tRNAs

Complementary base pairing takes place

between the mRNA codon and the anticodon of
the tRNA, and allows for the correct amino acids
to be added to the chain

When a ribosome reaches one of three stop

codons, translation ceases
28
 The Genetic Code

mRNA specifies an amino acid sequence using the

genetic code

There are 64 possible triplet codons, read in the 5¢

to 3¢ direction; each specifies one amino acid

There are 20 common amino acids; some amino

acids are specified by one codon and others by up
to six different codons

29
30
31
 7.1 DNA Is the Hereditary Molecule of Life

The term “hereditary molecule” means a

molecular substance that carries and conveys
the genetic information of a species

Long before DNA was known to be the

hereditary molecule, five essential
characteristics of hereditary material were
identified

32
 Features of Hereditary Material

1. Localized to the nucleus, component of

chromosomes

2. Present in stable form in cells

3. Sufficiently complex to contain information

needed for structure, function, development,
and reproduction of an organism
33
 Features of Hereditary Material, continued

4. Able to accurately replicate itself so that

daughter cells contain the same information
as parent cells

5. Mutable, undergoing a low rate of mutations

that introduces genetic variation and could
cause changes over time

34
 Chromosomes Contain DNA

DNA was first noticed in 1869 when Friedrich

Meischer isolated it from nuclei of white blood cells

He called it “nuclein”

In the 1870s, microscopic studies identified fusion

of male and female nuclei during reproduction and
chromosomes were observed soon after

35
Early Suggestion That DNA Was the Hereditary Material

In 1895, Edmund Wilson first suggested that DNA

might be the hereditary material

He observed that sperm and eggs contribute the

same number of chromosomes during reproduction

He made a connection between the substance

observed by Meischer and the chromatin of
chromosomes

36
 Rediscovery of Mendel

In 1900, Mendel’s hereditary principles were

rediscovered

In 1903, Walter Sutton and Theodor Boveri

independently described the parallels between
chromosome partitioning into gametes and the
inheritance of genes

37
 Focus on the Nucleus and Chromosomes

By 1920, DNA was identified as the principal

component of nuclein

The basic chemistry of DNA was deciphered

It is a polynucleotide consisting of four repeating

subunits, adenine (A), thymine (T), cytosine (C),
and guanine (G), held together by covalent
bonds
38
 DNA As the Candidate Hereditary Material

In 1923, DNA was localized to chromosomes and

made a candidate for the hereditary material

However, both proteins and RNA are also found

in chromosomes

Lipids and carbohydrates were also considered

to be candidates
39
 The Transformation Factor

Frederick Griffith identified two strains of

Pneumococcus: S, which caused fatal pneumonia in
mice, and R, which did not

A single nucleotide change can convert the R

(rough) strain into the S (smooth) strain

These strains occur in four antigenic types (I, II, III,

and IV) that cannot be altered by mutation alone
40
41
 Griffith’s Experimental Results

Mice infected with strain SIII developed pneumonia

and died

Mice infected with strain RII or with heat-killed

strain SIII survived

Mice infected with heat-killed strain SIII and live

strain RII developed pneumonia and died – live-
type SIII bacteria were recovered from the mice
42
43
 DNA Is the Transformation Factor

Griffiths had described the process of

transformation in his experiment

Biochemical tests of the heat-killed SIII extract

showed that it contained mainly DNA, with small
amounts of RNA, protein, lipids, and
polysaccharides

Additional tests were needed to identify the

transforming material
44
 Experimental Results

Avery, MacLeod, and McCarty used heat-killed SIII

bacteria and live RII bacteria and infected mice

The extract of heat-killed SIII bacteria was divided

into aliquots and treated to destroy either DNA,
RNA, proteins, or lipids and polysaccharides

All aliquots killed the mice except the one with the
DNA destroyed
45
46
 DNA Is the Hereditary Molecule

Hershey and Chase, in 1952, showed that DNA is

responsible for bacteriophage infection of bacteria
cells

Bacteriophages (phages) are viruses that infect

bacteria

Phages such as T2 have a protein shell with a tail

segment that attaches to the host cell and a head
that contains DNA
47
 Phage Infection of Bacteria

Phages must infect bacterial hosts to reproduce

Infection begins when the phage injects DNA into

the bacterial cell and leaves its protein shell on the
surface

The phage DNA replicates in the bacterium and

produces proteins that are assembled into progeny
phage – these are released by lysis of the host cell
48
49
 Hershey and Chase Experiments

Proteins contain large amounts of sulfur but almost

no phosphorus

DNA contains large amounts of phosphorus but no

sulfur

Hershey and Chase separately labeled either phage

proteins (with 35S) or DNA (with 32P) and then traced
each radioactive label in the course of infection
50
Phage DNA, Not Protein, Is Responsible for Infecting the
Bacteria

After infection, in both experiments, agitation by a

blender separated the empty phage particles from
the infected bacteria

In the protein labeling experiment, the radioactivity

was detected in the empty phage particles (ghosts)

In the DNA labeling experiment, the radioactivity

was detected inside the infected bacteria
51
52
 7.2 The DNA Double Helix Consists of Two
Complementary and Antiparallel Strands
Watson and Crick’s model of the secondary structure of
DNA shows that it is fairly simple in structure

It is composed of four kinds of nucleotides, joined by

covalent phosphodiester bonds with two
polynucleotide chains that come together to form a
double helix

Despite the structural simplicity, DNA is a complex

informational molecule
53
 DNA Nucleotides

A DNA nucleotide is composed of a sugar, one of four

nitrogenous bases, and up to three phosphate groups

Deoxyribose is the sugar of DNA nucleotides; it has five

carbons, identified as 1¢, 2¢, 3¢, 4¢ and 5¢

A nucleotide base is attached to the 1¢ carbon, an OH

(hydroxyl) group is attached to the 3¢ carbon,
and one to three phosphates are attached to the
5¢ carbon
54
55
56
 Two Types of DNA Bases

Pyrimidines, thymine or cytosine, have a single ring,

and purines, adenine or guanine, have a double ring

Deoxynucleotide monophosphates that are part of

a polynucleotide chain have single phosphates and
are called dNTPs, where N refers to any of the four
bases

Deoxynucleotide triphosphates, dNTPs, are not part

of a polynucleotide chain
57
 Assembly of Polynucleotide Chains

Individual nucleotides are assembled into chains by

the enzyme DNA polymerase

It catalyzes the formation of a phosphodiester bond

between the 3¢ hydroxyl group of one nucleotide
and the 5¢ phosphate of an adjacent one

Each polynucleotide chain has a sugar-phosphate

backbone, consisting of alternating sugar and
phosphate groups
58
59
60
 Complementary DNA Nucleotide Pairing

The two polynucleotide chains of a double helix

form a stable structure that follows two rules:

1. The bases of one strand are complementary to the

bases in the corresponding strand (A pairs with T and
G pairs with C)

1. The two strands are antiparallel, with respect to their

5¢ and 3¢ ends (Ex: 5’ ATCG 3’ comp 3’ TAGC 5’)

61
 Basis of Complementary Pairing

Complementary base pairing combines one purine

with one pyrimidine

The chemical basis of the pairing is the formation of

stable hydrogen (H) bonds between the bases on
the antiparallel strands

Two H bonds form between A and T; three H bonds

form between G and C

62
63
 Antiparallel Orientation

The antiparallel arrangement of the two strands of

the double helix is essential for forming stable
H bonds

It brings the partial charges of complementary

nucleotides into alignment

If two strands were to align in parallel, the charges

of complementary nucleotides would repel each
other
64
 The Twisting Double Helix

The DNA double helix has an axis of helical

symmetry, an imaginary line that passes lengthwise
through the core of the helix

The diameter of the molecule is 20Å, where 1Å is

10-10 m (REALLY SMALL!!!)

The diameter results from the fact that each

complementary base pair (A and T or G and C) is 20Å
wide
65
66
 Nucleotide Base Stacking

Nucleotide base pairs are spaced along the DNA

duplex at intervals of 3.4Å

This tight packing leads to base stacking, the

offsetting of adjacent base pairs so that their planes
are parallel

This leads to a twist in the double helix

67
68
 Major and Minor Grooves

Base-pair stacking creates gaps between the sugar

phosphate backbones that partially expose the
nucleotides

The major groove, approximately 12Å wide,

alternates with the minor groove, approximately
6Å wide

These grooves are regions where DNA binding

proteins can make direct contact with nucleotides
69
70
 7.3 DNA Replication Is Semiconservative and
Bidirectional

The integrity of the nucleotide sequence of DNA

is of paramount important

The general mechanism of DNA replication is the

same in all organisms

As organisms diverged and became more

complex, some differences did develop in the
replication proteins and enzymes
71
 Three Attributes of DNA Replication Shared by All
Organisms
1. Each strand of the parental DNA molecule
remains intact during replication

2. Each parental strand serves as a template for

formation of an antiparallel, complementary
daughter strand

3. Completion of replication results in the formation

of two identical daughter duplexes composed of
one parental and one daughter strand
72
 Three Competing Models of Replication

Semiconservative DNA replication: each daughter

duplex contains one parental and one daughter
strand

73
 Origin of Replication in Bacterial DNA

DNA replication is most often bidirectional,

proceeding in both directions from a single origin
of replication in bacterial chromosomes

Eukaryotic chromosomes have multiple origins of

replication

John Cairns reported the first evidence of

bacterial origins of replication in 1963

74
 Cairns’ Observations

Cairns grew bacteria in a medium containing 3H-

thymine

He extracted the bacterial chromosomes during

replication and placed them on x-ray film

The autoradiographs showed dark lines that

revealed the pattern of replicating DNA molecules –
these were called theta structures (q structures)
75
76
 Evidence of Bidirectional DNA Replication

The theta structures Cairns observed are consistent with

both unidirectional and bidirectional replication

In bidirectional DNA replication, new DNA is

synthesized in both directions from the single origin,
creating an expanding replication bubble

At each end of the replication bubble is a replication

fork; replication is complete when the replication forks
meet
77
78
 Multiple Replication Origins in Eukaryotes

Autoradiograph analysis shows multiple origins of

replication on eukaryotic chromosomes
Large eukaryotic genomes contain thousands of
origins of replication separated by 40,000 to 50,000
base pairs
The human genome contains more than 10,000
origins
DNA replication rate varies among different types of
cells

79
Multiple origins of replication on a single chromosome of the fly

80
 Nucleosome
(10 nm in diameter)
DNA
double helix
(2 nm in diameter)
H1
Histones
Histone tail

DNA, the double helix Histones Nucleosomes, or “beads

on a string” (10-nm fiber)
 Chromatid
(700 nm)

30-nm fiber

Loops Scaffold

300-nm fiber

Replicated
chromosome
(1,400 nm)

30-nm fiber Looped domains Metaphase

(300-nm fiber) chromosome
 7.4 DNA Replication Precisely Duplicates the
Genetic Material

Replication is best studied in bacteria (E. Coli)

Replication has similarity and differences between
Bacteria, Archaea, and Eukarya,
The enzymes and proteins involved are parts of large
complex aggregations of proteins and enzymes
called replisomes
These assemble at each replication fork

83
 DNA Sequences at Replication Origins

Replication origins have sequences that attract

replication enzymes

The origin of replication sequence of E. coli is

called oriC, and it contains about 245 bp of A-T
rich DNA

The origin is divided into three 13-bp sequences

followed by four 9-bp sequences

84
85
 Bacterial Replication Origins

Replication origins of bacterial species have similar

(conserved) but not identical sequences

Comparison between species leads to identification

of consensus sequences, the nucleotides found
most often at each position of DNA in the conserved
region

The 13-mer and 9-mer sequences of oriC are

conserved—they play an essential role in replication
86
 Eukaryote Replication Origins

Saccharomyces cerevisiae (yeast) has the most fully

characterized origin-of-replication sequences

The multiple origins of replication are called

autonomously replicating sequences (ARS)

ARS organization and sequence is similar throughout

the yeast genome

Replication origins of other eukaryotes are less well

characterized
87
88
 Replication Initiation in Bacteria

Replication in E. coli requires that replication-

initiating enzymes locate and bind to oriC
consensus sequences

Enzymes DnaA, DnaB, DnaC bind at oriC and

initiate DNA replication

DnaA binds first, bends the DNA, and breaks

hydrogen bonds in the A-T rich sequences

89
 Initiation of Replication

DnaA first binds the 9-mer sequences, bends the

DNA, and breaks hydrogen bonds in the A-T rich
sequences of the 13-mer region

DnaB is a helicase that uses ATP energy to break

hydrogen bonds of complementary bases to
separate the strands and unwind the helix

DnaB is carried to the DNA helix by DnaC

90
91
 Initiation of Replication, continued

The unwound DNA strands are kept from

reannealing by single-stranded binding protein (SSB)

Unwinding of circular chromosomes will create

torsional stress, potentially leading to
supercoiled DNA

Enzymes called topoisomerases catalyze controlled

cleavage and rejoining of DNA that prevents
overwinding
92
93
 RNA Primers Are Needed for DNA Replication

DNA polymerase elongates DNA strands by adding

nucleotides to the 3¢ end of a pre-existing strand
They cannot initiate DNA strand synthesis on their
own
RNA primers are needed; these are synthesized by a
specialized RNA polymerase called primase
Primase and some additional proteins join DnaA at
oriC to form the primosome
94
Continuous and Discontinuous Strand Replication

In E. coli, daughter DNA strands are synthesized

by the DNA polymerase III (pol III) holoenzyme

Holoenzyme refers to a multiprotein complex in

which a core enzyme is associated with the
additional components needed for full function

The replisome is found at each replication fork

and contains two copies of pol III

95
 Leading and Lagging Strand Synthesis

One copy of pol III synthesizes one daughter strand

continuously in the same direction as fork
progression
This is the leading strand
The other copy of pol III elongates the daughter
strand discontinuously, in the opposing direction to
fork progression, via short segments (Okazaki
fragments)
This is the lagging strand
96
 Overview
Origin of replication
Leading strand Lagging strand

Primer

Lagging strand Leading strand

Overall directions
of replication
Origin of replication

3¢
5¢
5¢ RNA primer
“Sliding clamp”
3¢
5¢ DNA poll III
Parental DNA

3¢
5¢

5¢
3¢

5¢
 Overview
Origin of replication
Leading strand Lagging strand

Primer

Lagging strand Leading strand

Overall directions
of replication
 Origin of replication

3¢
5¢
5¢ RNA primer
“Sliding clamp”
3¢
5¢ DNA pol III
Parental DNA

3¢
5¢

5¢
3¢

5¢
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
 Overview
Origin of replication
Leading strand Lagging strand

Lagging strand
2
1
Leading strand
Overall directions
of replication

3¢ 5¢

5¢ 3¢
Template
strand

3¢ RNA primer
5¢
3¢
1
5¢

Okazaki 3¢
fragment 5¢
3¢
1
5¢

5¢
3¢

3¢
2 1 5¢

5¢
3¢

3¢
5¢
2 1

5¢
3¢

3¢
1 5¢
2

Overall direction of replication

 Overview
Origin of replication
Leading strand Lagging strand

Lagging strand
2
1
Leading strand
Overall directions
of replication
 3¢ 5¢

5¢ 3¢
Template
strand
 3¢ 5¢

5¢ 3¢
Template
strand

3¢ 5¢
RNA primer 3¢
1
5¢
 3¢ 5¢

5¢ 3¢
Template
strand

3¢ 5¢
RNA primer 3¢
1
5¢

Okazaki 3¢
fragment 5¢
3¢
1
5¢
 3¢ 5¢

5¢ 3¢
Template
strand

3¢ 5¢
RNA primer 3¢
1
5¢

Okazaki 3¢
fragment 5¢
3¢
5¢ 1
3¢ 5¢

3¢
2 1 5¢
 3¢ 5¢

5¢ 3¢
Template
strand

3¢ 5¢
RNA primer 3¢
1
5¢

Okazaki 3¢
fragment 5¢
3¢
5¢ 1
3¢ 5¢

3¢
2 1 5¢

5¢
3¢

3¢
5¢
2 1
 3¢ 5¢

5¢ 3¢
Template
strand

3¢ 5¢
RNA primer 3¢
1
5¢

Okazaki 3¢
fragment 5¢
3¢
5¢ 1
3¢ 5¢

3¢
2 1 5¢

5¢
3¢

3¢
5¢
2 1

5¢
3¢

3¢
1 5¢
2

Overall direction of replication

111
 RNA Primer Removal and Okazaki Fragment Ligation

DNA polymerase I (pol I) uses two activities to

complete replication:
– Its 5¢ to 3¢ exonuclease activity removes the RNA
primers
– Its 5¢ to 3¢ polymerase activity adds DNA nucleotides to
the 3¢ end of the DNA segment preceding the primer

DNA ligase seals the gap between the resulting

DNA segments

112
113
114
115
Simultaneous Synthesis of Leading and Lagging Strands

Each replisome complex carries out replication of

the leading and lagging strand simultaneously

The DNA pol III holoenzyme contains 11 protein

subunits, with the two pol III core polymerases each
tethered to a different copy of the tau (t) protein

The tau proteins are joined to a protein complex

called the clamp loader; two additional proteins
form the sliding clamp
116
117
 The Sliding Clamp

The sliding clamp can close around the double-

stranded DNA during replication

It has a “doughnut hole” of about 35Å, into which

the DNA fits

The sliding clamp anchors the DNA pol III core

enzyme to the template

It is required for the high level of pol III activity

118
119
120
121
122
 DNA Proofreading

DNA replication is very accurate, mainly because

DNA polymerases undertake DNA proofreading,
to correct occasional errors

Errors in replication occur about one every billion

nucleotides in E. coli

Proofreading ability of DNA polymerase enzymes

is due to a 3¢ to 5¢ exonuclease activity

123
 Proofreading

Replication errors produce a DNA mismatch, and

inability of the mismatched bases to form the
appropriate H-bonds

This leads to displacement of the 3¢-OH into the

3¢ to 5¢ exonuclease “site” of the enzyme

Several nucleotides (including the incorrect one)

are removed and new nucleotides incorporated

124
125
 Eukaryotic DNA Polymerases

Eukaryotes have many more DNA polymerases than

bacteria

DNA polymerase a carries out synthesis of RNA

primers

Polymerase d and polymerase e carry out lagging

and leading strand synthesis, respectively

Each interacts with proliferating cell nuclear antigen

(PCNA)
126
Eukaryotic Replication Has Similarities and Differences
with Bacterial Replication

Numerous replication proteins and enzymes in

eukaryotes perform functions similar to those in
bacteria, such as

– PCNA operates as the sliding clamp in eukaryotic

replication

– A DNA helicase unwinds the DNA at replication origins and

DNA ligases join Okazaki fragments

The eukaryotic genome has early and late replicating

regions and their regulation is not fully understood
127
128
 Telomeres

The leading strand of linear chromosomes can be

replicated to the end

The lagging strand requirement for a primer means

that lagging strands cannot be completely replicated

This problem is resolved by repetitive sequences at

the ends of chromosomes, called telomeres

These repeats ensure that incomplete chromosome

replication does not affect vital genes
129
130
 Telomerase

Telomeres are synthesized by the

ribonucleoprotein telomerase

Blackburn, Greider, and Szostak received the 2009

Nobel Prize for the discovery of telomeres and
telomerase

The RNA in telomerase is complementary to the

telomere repeat sequence and acts as a template
for addition of DNA
131
 Telomerase Function

The template RNA of telomerase allows new DNA

replication, to lengthen the telomere sequences

Once telomeres are sufficiently elongated, the a

polymerase synthesizes additional RNA primers

New DNA replication then fills out the chromosome

ends

Telomere sequences in most organisms are quite

similar
132
133
 Importance of Telomerase Activity

Mice that are homozygous for loss-of-function

mutations of the TERT (telomerase reverse
transcriptase) gene give rise to developmental defects

The defects are first observed in the fourth and fifth

generations, due to loss of telomere length with each
generation

By the fourth and fifth generations, shortening of

chromosomes is critical and apoptosis is induced
134
 Telomeres, Aging, and Cancer

Telomere length is important for chromosome

stability, cell longevity, and reproductive success

Telomerase is active in germ-line cells and some

stem cells in eukaryotes

Differentiated somatic cells and cells in culture have

virtually no telomerase activity; such cells have
limited life spans (30 to 50 cell divisions)

135
 Werner Syndrome

Telomerase inactivity is associated with normal

aging of cells

A condition known as Werner syndrome causes

early onset of some features of aging

A mutation in RECQL2, a gene encoding a

helicase required for telomerase activity, is the
cause of Werner syndrome

136
 Dyskeratosis Congenita

Dyskeratosis congenita is a disorder associated

with a loss of function of a gene, DKC1, that
encodes a protein needed for normal telomerase
function

Patients with this disorder have skin and nail

abnormalities, loss of vision and hearing, and
abnormalities of blood cell formation

137
 Abnormal Reactivation of Telomerase Activity

Telomerase is normally turned off in somatic cells

Reactivation of telomerase can lead to aging cells

that continue to proliferate, a feature of many
types of cancer

TERT reactivation is one of the most common

mutations in cancers of all types

138