Download LE 01-10b

Figure 19-01
LE 19-2
2 nm
DNA double helix
Histones
Histone
tails
Histone H1
Linker DNA
(“string”)
10 nm
Nucleosome
(“bead”)
Nucleosomes (10 nm fiber)
30 nm
Nucleosome
30-nm fiber
Protein scaffold
Loops
300 nm
Looped domains (300-nm fiber)
700 nm
1,400 nm
Metaphase chromosome
Scaffold
LE 19-3
Signal
NUCLEUS
Chromatin
Chromatin modification:
DNA unpacking involving
histone acetylation and
DNA demethylation
DNA
Gene available
for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Intro
RNA processing
Tail
Cap
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypeptide
Cleavage
Chemical modification
Transport to cellular
destination
Active protein
Degradation of protein
Degraded protein
LE 19-4
Histone
tails
DNA
double helix
Amino acids
available
for chemical
modification
Histone tails protrude outward from a nucleosome
Unacetylated histones
Acetylated histones
Acetylation of histone tails promotes loose chromatin
structure that permits transcription
LE 19-5
Enhancer
(distal control elements)
Proximal
control elements
Exon
Intron
Exon
Poly-A signal Termination
sequence
region
Intron Exon
DNA
Upstream
Downstream
Promoter
Primary RNA
transcript
5
(pre-mRNA)
Transcription
Exon
Intron
Intron RNA
Poly-A signal
Exon
Intron Exon
Cleaved 3 end
of primary
transcript
RNA processing:
Cap and tail added;
introns excised and
exons spliced together
Coding segment
mRNA
3
5 Cap
5 UTR
(untranslated
region)
Start
codon
Stop
codon
Poly-A
3 UTR
(untranslated tail
region)
LE 19-6
Distal control
element
Activators
Promoter
Gene
DNA
TATA
box
Enhancer
General
transcription
factors
DNA-bending
protein
Group of
mediator proteins
RNA
polymerase II
RNA
polymerase II
Transcription
Initiation complex
RNA synthesis
LE 19-7
Liver cell
nucleus
Available
activators
Enhancer
Control
elements
Lens cell
nucleus
Available
activators
Promoter
Albumin
gene
Crystallin
gene
Albumin
gene not
expressed
Albumin
gene
expressed
Crystallin gene
not expressed
Liver cell
Crystallin gene
expressed
Lens cell
LE 19-8
Exons
DNA
Primary
RNA
transcript
RNA splicing
mRNA
or
LE 19-9
Protein
complex
Degradation of mRNA
Dicer
OR
miRNA
Target mRNA
Hydrogen
bond
Blockage of translation
LE 19-10
Proteasome
and ubiquitin
to be recycled
Ubiquitin
Proteasome
Protein to
be degraded
Ubiquitinated
protein
Protein entering a
proteasome
Protein
fragments
(peptides)
LE 19-11
Proto-oncogene
DNA
Translocation or transposition:
gene moved to new locus,
under new controls
Gene amplification:
multiple copies of the gene
New
promoter
Normal growth-stimulating
protein in excess
Point mutation
within a control
element
Oncogene
Normal growth-stimulating
protein in excess
Normal growth-stimulating
protein in excess
Point mutation
within the gene
Oncogene
Hyperactive or
degradationresistant protein
LE 19-12_3
MUTATION
Growth
factor
Hyperactive
Ras protein
(product of
oncogene)
issues signals
on its own
G protein
Cell cycle-stimulating
pathway
Receptor
Protein kinases
(phosphorylation
cascade)
NUCLEUS
Transcription
factor (activator)
DNA
Gene expression
Protein that
stimulates
the cell cycle
Cell cycle-inhibiting
pathway
Protein kinases
MUTATION
Defective or
missing
transcription
factor, such as
p53, cannot
activate
transcription
Active
form
of p53
UV
light
DNA damage
in genome
DNA
Protein that
inhibits
the cell cycle
Effects of
mutations
EFFECTS OF MUTATIONS
Protein overexpressed
Cell cycle overstimulate
Protein absent
Increased cell
division
Cell cycle not
inhibited
LE 19-13
Colon
Normal colon
epithelial cells
Loss of
tumorsuppressor
gene p53
Activation of
ras oncogene
Loss of
tumorsuppressor
Colon wall gene APC (or
other)
Small benign
growth (polyp)
Loss of
tumorsuppressor
gene DCC
Additional
mutations
Larger benign
growth (adenoma)
Malignant tumor
(carcinoma)
LE 19-13a
Colon
Loss of
tumorsuppressor
Colon wall gene APC (or
other)
Normal colon
epithelial cells
Small benign
growth (polyp)
LE 19-13b
Small benign
growth (polyp)
Activation of
ras oncogene
Loss of
tumorsuppressor
gene p53
Loss of
tumorsuppressor
gene DCC
Additional
mutations
Larger benign
growth (adenoma)
Malignant tumor
(carcinoma)
Figure 19-15
LE 19-16
Transposon
New copy of
transposon
DNA of genome
Transposon
is copied
Insertion
Mobile transposon
Transposon movement (“copy-and-paste” mechanism)
Retrotransposon
New copy of
retrotransposon
DNA of genome
RNA
Insertion
Reverse
transcriptase
Retrotransposon movement
LE 19-16a
Transposon
New copy of
transposon
DNA of genome
Transposon
is copied
Mobile transposon
Transposon movement (“copy-and-paste” mechanism)
Insertion
LE 19-16b
Retrotransposon
New copy of
retrotransposon
DNA of genome
RNA
Insertion
Reverse
transcriptase
Retrotransposon movement
LE 19-17a
DNA
RNA transcripts
Non-transcribed
spacer
Transcription unit
DNA
18S
5.8S
28S
rRNA
5.8S
28S
18S
Part of the ribosomal RNA gene family
LE 19-17b
-Globin
Heme
Hemoglobin
a-Globin
a-Globin gene family
-Globin gene family
Chromosome 11
Chromosome 16

Embryo
 a a1 a2 a1
Fetus
and adult
 A
Embryo

Fetus
The human a-globin and -globin gene families


Adult
LE 19-19
Ancestral globin gene
Duplication of
ancestral gene
Mutation in
both copies
a
Transposition
to different
chromosomes

a
Further
duplications
and mutations




a
 a a1 a2
a1 
a-Globin gene family
on chromosome 16


A


-Globin gene family
on chromosome 11

LE 19-20
EGF
EGF
EGF
EGF
Epidermal growth
factor gene with multiple
EGF exons (green)
Exon
shuffling
F
F
F
Fibronectin gene with multiple
“finger” exons (orange)
F
F
EGF
Exon
duplication
K
K
Plasminogen gene with a
“kringle” exon (blue)
Portions of ancestral genes
Exon
shuffling
TPA gene as it exists today
K