Figure 19-01

LE 19-2

DNA double helix

Histonetails

His-tones

Linker DNA(“string”)

Nucleosome(“bead”)

10 nm

2 nm

Histone H1

Nucleosomes (10 nm fiber)

30 nm

Nucleosome

30-nm fiber

300 nm

Loops

Scaffold

Protein scaffold

Looped domains (300-nm fiber)

Metaphase chromosome

700 nm

1,400 nm

LE 19-2a

DNA double helix

Histonetails

His-tones

Linker DNA(“string”)

Nucleosome(“bead”)

10 nm

2 nm

Histone H1

Nucleosomes (10-nm fiber)

LE 19-2b

30 nm

Nucleosome

30-nm fiber

LE 19-2c

300 nm

Loops

Scaffold

Protein scaffold

Looped domains (300-nm fiber)

LE 19-2d

Metaphase chromosome

700 nm

1,400 nm

LE 19-3Signal

NUCLEUS

DNA

RNA

Chromatin

Gene availablefor transcription

Gene

Exon

Intro

Transcription

Primary transcript

RNA processing

Cap

Tail

mRNA in nucleus

Transport to cytoplasm

CYTOPLASM

mRNA in cytoplasm

Translation

Degradationof mRNA

Polypeptide

CleavageChemical modificationTransport to cellular

destination

Degradation of protein

Active protein

Degraded protein

Chromatin modification:DNA unpacking involvinghistone acetylation and

DNA demethylation

LE 19-4

Histonetails

Amino acidsavailablefor chemicalmodification

DNAdouble helix

Histone tails protrude outward from a nucleosome

Acetylation of histone tails promotes loose chromatinstructure that permits transcription

Unacetylated histones Acetylated histones

LE 19-4a

Histonetails

Amino acidsavailablefor chemicalmodification

DNAdouble helix

Histone tails protrude outward from a nucleosome

LE 19-4b

Acetylation of histone tails promotes loose chromatinstructure that permits transcription

Unacetylated histones Acetylated histones

LE 19-5

Enhancer(distal control elements)

Proximal control elements

Upstream

DNA

Promoter

Exon Intron Exon Intron Exon

DownstreamTranscription

Poly-A signalsequence

Terminationregion

Intron Exon Intron Exon

RNA processing:Cap and tail added;introns excised andexons spliced together

Poly-A signal

Cleaved 3′ endof primarytranscript

3′

Poly-Atail

3′ UTR(untranslated

region)

5′ UTR(untranslated

region)

Startcodon

Stopcodon

Coding segment

Intron RNA

5′ Cap

mRNA

Primary RNAtranscript(pre-mRNA)

5′Exon

LE 19-6

Distal controlelement Activators

Enhancer

DNA

DNA-bendingprotein

TATAbox

PromoterGene

Generaltranscriptionfactors

Group ofmediator proteins

RNApolymerase II

RNApolymerase II

RNA synthesisTranscriptionInitiation complex

LE 19-7

Controlelements

Enhancer Promoter

Albumingene

Crystallingene

Availableactivators

Availableactivators

Albumingene notexpressed

Albumingeneexpressed

Liver cell Lens cell

Crystallin genenot expressed Crystallin gene

expressed

Liver cellnucleus

Lens cellnucleus

LE 19-8

PrimaryRNAtranscript

DNA

or

Exons

RNA splicing

mRNA

LE 19-9

Dicer

Hydrogenbond

Proteincomplex

miRNATarget mRNA

Degradation of mRNA

OR

Blockage of translation

LE 19-10

Protein tobe degraded

Ubiquitinatedprotein

Proteasome

Protein entering aproteasome

Protein fragments(peptides)

Proteasomeand ubiquitinto be recycled

Ubiquitin

LE 19-11

Proto-oncogene

DNA

Translocation or transposition:gene moved to new locus, under new controls

Newpromoter

Gene amplification:multiple copies of the gene

Point mutationwithin a controlelement

Oncogene Oncogene

Point mutationwithin the gene

Normal growth-stimulatingprotein in excess

Normal growth-stimulatingprotein in excess Normal growth-stimulating

protein in excessHyperactive ordegradation-resistant protein

LE 19-12_1

Cell cycle-stimulatingpathway

Growthfactor

G protein

Receptor

MUTATION

Protein kinases(phosphorylationcascade)

NUCLEUS

HyperactiveRas protein(product of oncogeneissues signalson its own.

Transcriptionfactor (activator)

DNA

Gene expression

Protein thatstimulatesthe cell cycle

LE 19-12_2

Activeformof p53

DNADNA damagein genome

UVlight

Protein kinasesMUTATION

Defective ormissingtranscriptionfactor, such as p53, cannotactivatetranscription

Protein kinases(phosphorylationcascade)

Cell cycle-inhibitingpathway

Cell cycle-stimulatingpathway

Protein thatstimulatesthe cell cycle

NUCLEUS

DNA

Gene expression

Transcriptionfactor (activator)

Receptor

G protein

Growthfactor

MUTATIONHyperactiveRas protein(product ofoncogene)issues signalson its own

Protein thatinhibitsthe cell cycle

LE 19-12_3

Protein overexpressed

EFFECTS OF MUTATIONS

Protein absent

Cell cycle notinhibited

Increased celldivision

Cell cycle overstimulate

Effects ofmutations

Activeformof p53

DNADNA damagein genome

UVlight

Protein kinasesMUTATION

Defective ormissingtranscriptionfactor, such as p53, cannotactivatetranscription

Protein kinases(phosphorylationcascade)

Cell cycle-inhibitingpathway

Cell cycle-stimulatingpathway

Protein thatinhibitsthe cell cycle

NUCLEUS

DNA

Gene expression

Transcriptionfactor (activator)

Receptor

G protein

Growthfactor

MUTATIONHyperactiveRas protein(product ofoncogene)issues signalson its own

Protein thatstimulatesthe cell cycle

LE 19-13

Colon

Colon wall

Loss oftumor-suppressorgene APC (orother)

Normal colonepithelial cells

Small benigngrowth (polyp)

Larger benigngrowth (adenoma)

Activation ofras oncogene

Loss oftumor-suppressorgene DCC

Loss oftumor-suppressorgene p53

Additionalmutations

Malignant tumor(carcinoma)

LE 19-14Exons (regions of genes coding

for protein, rRNA, or tRNA) (1.5%)

Alu elements (10%)

Simple sequenceDNA (3%)

Large-segmentduplications (5–6%)

UniquenoncodingDNA (15%)

Introns andregulatorysequences(24%)

RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)

RepetitiveDNA unrelated totransposableelements(about 15%)

Figure 19-15

LE 19-16

DNA of genomeTransposon

is copied

Mobile transposon

Transposon

Insertion

New copy oftransposon

Transposon movement (“copy-and-paste” mechanism)

Retrotransposon movement

DNA of genome

Insertion

RNA

Reversetranscriptase

RetrotransposonNew copy of

retrotransposon

LE 19-16a

DNA of genomeTransposon

is copied

Mobile transposon

Transposon

Insertion

New copy oftransposon

Transposon movement (“copy-and-paste” mechanism)

LE 19-16b

Retrotransposon movement

DNA of genome

Insertion

RNA

Reversetranscriptase

RetrotransposonNew copy of

retrotransposon

LE 19-17

DNA

Non-transcribedspacer

RNA transcripts

Transcription unit

DNA18S 5.8S 28S

rRNA

18S

5.8S28S

Part of the ribosomal RNA gene family

Heme

Hemoglobin

α-Globin

β-Globin

α-Globin gene family β-Globin gene family

Chromosome 11Chromosome 16

ζ ψζ ψα2 ψα1 α1α2ψβ δ βGγ∍ Aγ

Embryo Embryo Fetus AdultFetus

and adult

The human α-golbin and β-globin gene families

LE 19-17a

DNA

Non-transcribedspacer

RNA transcripts

Transcription unit

DNA18S 5.8S 28S

rRNA

18S

5.8S28S

Part of the ribosomal RNA gene family

LE 19-17b

Heme

Hemoglobin

α-Globin

β-Globin

α-Globin gene family β-Globin gene family

Chromosome 11Chromosome 16

ζ ψζ ψα2 ψα1 α1α2ψβ δ βGγ∍ Aγ

Embryo Embryo Fetus AdultFetus

and adult

The human α-globin and β-globin gene families

LE 19-18

Nonsisterchromatids

Transposableelement

Gene

Crossover

Incorrect pairingof two homologuesduring meiosis

and

LE 19-19

Duplication ofancestral gene

Mutation inboth copies

Transpositionto differentchromosomes

Furtherduplicationsand mutations

Ancestral globin gene

ζ ψζ ψα2 ψα1 α1α2ψβ δ βGγ∍ Aγ

α-Globin gene familyon chromosome 16

ψϑ

β-Globin gene familyon chromosome 11

ζ α

α

α β

β

∍ βγ

Evolu

tionary

tim

e

Table 19-1

LE 19-20

Epidermal growthfactor gene with multipleEGF exons (green)

EGF EGF EGF EGF

F F F F

Fibronectin gene with multiple“finger” exons (orange)

K

K KEGFF

Plasminogen gene with a“kringle” exon (blue)

Portions of ancestral genes TPA gene as it exists today

Exonshuffling

Exonshuffling

Exonduplication