1. CONTROL OF GENE EXPRESSION
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2. Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes
Gene regulation is the turning on and off of genes.
Gene expression is the overall process of information flow from genes to proteins.
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3. Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes
A cluster of genes with related functions, along with the control sequences, is called an operon.
Found mainly in prokaryotes.
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4. Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes
When an E. coli encounters lactose, all enzymes needed for its metabolism are made at once using the lactose operon.
The lactose (lac) operon includes
Three adjacent lactose-utilization genes
A promoter sequence where RNA polymerase binds and initiates transcription of all three lactose genes
An operator sequence where a repressor can bind and block RNA polymerase action.
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5. Proteins interacting with DNA turn prokaryotic genes on or off in response to environmental changes
Regulation of the lac operon
A regulatory gene, located outside the operon, codes for a repressor protein, that is always being transcribed & translated.
In the absence of lactose, the repressor binds to the operator and prevents RNA polymerase action.
Lactose inactivates the repressor, so
The operator is unblocked
RNA polymerase can bind to the promoter, and
all three genes of the operon are transcribed.
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6. Operon turned off (lactose is absent): OPERON Regulatory gene
Promoter
Operator
Lactose-utilization genes
DNA
mRNA
RNA polymerase cannot attach to the promoter
Protein
Active repressor
Operon turned on (lactose inactivates the repressor):
Figure 11.1B The lac operon
DNA
RNA polymerase is bound to the promoter
mRNA
Translation
Protein
Inactive repressor
Lactose
Enzymes for lactose utilization 6

7. Multiple mechanisms regulate gene expression in eukaryotes
Multiple control points exist in Eukaryotic gene expression
Genes can be turned on or off, or sped up, or slowed down.
These control points are like a series of pipes carrying water from your local water supply to a faucet in your home. Valves in this series of pipes are like the control points in gene expression.
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8. Multiple mechanisms regulate gene expression in eukaryotes
These control points include:
Chromosome changes and DNA unpacking
Control of transcription
Control of RNA processing including the
addition of a cap and tail and
splicing
Flow through the nuclear envelope
Breakdown of mRNA
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9. Multiple mechanisms regulate gene expression in eukaryotes
control of translation
control after translation including
cleavage/modification/activation of proteins and
breakdown of protein
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10. DNA unpacking Other changes to the DNA
Chromosome
Chromosome
DNA unpacking Other changes to the DNA
DNA
Gene
Gene
Transcription
Exon
RNA transcript
Intron
Addition of a cap and tail
Figure 11.7_1 The gene expression “pipeline” in a eukaryotic cell (part 1)
Splicing
Tail
Cap
mRNA in nucleus
Flow through nuclear envelope
NUCLEUS
CYTOPLASM 10

11. Chromosome structure and chemical modifications can affect gene expression
Eukaryotic chromosomes undergo multiple levels of folding and coiling, called DNA packing.
Nucleosomes are formed when DNA is wrapped around histone proteins.
Nucleosomes appear as “beads on a string”.
Each nucleosome bead includes DNA plus eight histones.
Stretches of DNA, called linkers, join consecutive nucleosomes.
At the next level of packing, the beaded string is wrapped into a tight helical fiber (30nm).
This fiber coils further into a thick supercoil (300nm).
Looping and folding further compacts DNA into a metaphase chromosome
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12. DNA double helix (2-nm diameter)
Metaphase chromosome
Nucleosome (10-nm diameter)
Tight helical fiber (30-nm diameter)
Linker
“Beads on a string”
Figure 11.2A DNA packing in a eukaryotic chromosome
Supercoil (300-nm diameter)
Histones
700 nm 12

13. Chromosome structure and chemical modifications can affect gene expression
DNA packing can prevent gene expression by preventing RNA polymerase & other proteins from contacting the DNA.
Cells seem to use higher levels of packing for long-term inactivation of genes.
Highly compacted chromatin is generally not expressed
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14. Chromosome structure and chemical modifications can affect gene expression
Chemical modification of DNA bases or histone proteins can result in epigenetic inheritance.
Enzymes can add a methyl group to DNA bases, w/o changing the sequence of the bases.
Genes are not expressed when methylated
Removal of the extra methyl groups can turn on some of these genes
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15. Chromosome structure and chemical modifications can affect gene expression
X-chromosome inactivation
In female mammals either the maternal or paternal chromosome is randomly inactivated.
occurs early in embryonic development; all cellular descendants have the same inactivated chromosome.
An inactivated X chromosome = Barr body.
Tortoiseshell fur coloration is due to inactivation of X chromosomes in heterozygous female cats.
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16. Cell division and random X chromosome inactivation
Early Embryo
Adult
Two cell populations
Cell division and random X chromosome inactivation
X chromo- somes
Active X
Orange fur
Inactive X
Figure 11.2B A tortoiseshell pattern on a female cat, a result of X chromosome inactivation
Allele for orange fur
Inactive X
Allele for black fur
Active X
Black fur 16

17. Complex assemblies of proteins control eukaryotic transcription
Prokaryotes and eukaryotes employ regulatory proteins (activators and repressors) that
bind to specific segments of DNA
either promote or block the binding of RNA polymerase, turning the transcription of genes on and off.
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18. Complex assemblies of proteins control eukaryotic transcription
Eukaryotic RNA polymerase requires the assistance of proteins = transcription factors.
Transcription Factors Include:
Activator proteins bind to DNA sequences (enhancers) and initiate gene transcription. Binding of activators leads to bending of the DNA.
Other transcription factors interact with bound activators, then bind as a complex to the gene’s promoter.
Then RNA polymerase binds the promoter transcription begins.
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19. Transcription factors
Enhancers
Promoter
Gene
DNA
Activator proteins
Transcription factors
Other proteins
RNA polymerase
Figure 11.3 A model for the turning on of a eukaryotic gene
Bending of DNA
Transcription 19

20. Cleavage, modification, activation
Figure 11.7_2
CYTOPLASM
mRNA in cytoplasm
Breakdown of mRNA
Broken- down mRNA
Translation
Polypeptide
Polypeptide
Cleavage, modification, activation
Active protein
Active protein
Figure 11.7_2 The gene expression “pipeline” in a eukaryotic cell (part 2)
Breakdown of protein
Amino acids 20

21. Small RNAs play multiple roles in controlling gene expression
microRNAs (miRNAs) can bind to complementary sequences on mRNA molecules either
degrading the target mRNA or
blocking its translation
RNA interference (RNAi) is the use of miRNA to artificially control gene expression by injecting miRNAs into a cell to turn off a specific gene sequence.
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22. miRNA- protein complex1
miRNA- protein complex 2
Target mRNA
Figure 11.5 Mechanisms of RNA interference 3 or 4
Translation blocked
mRNA degraded 22

23. Initial polypeptide (inactive) Folded polypeptide (inactive)SH SH
Folding of the polypeptide and the formation of S—S linkages S S S S S
Cleavage SH S SH SH S S SH S S S S
Initial polypeptide (inactive)
Folded polypeptide (inactive)
Active form of insulin
Figure 11.6 Protein activation: the role of polypeptide cleavage 23

24. CLONING OF PLANTS AND ANIMALS
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25. Plant cloning shows that differentiated cells may retain all of their genetic potential
Most differentiated cells retain a full set of genes, even though only a subset may be expressed. Evidence is available from
plant cloning, in which a root cell can divide to form an adult plant
salamander limb regeneration, in which the cells in the leg stump dedifferentiate, divide, and then redifferentiate, giving rise to a new leg.
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26. Root cells cultured in growth medium Cell division in culture
Root of carrot plant
Single cell
Figure Growth of a carrot plant from a differentiated root cell
Root cells cultured in growth medium
Cell division in culture
Plantlet
Adult plant 26

27. Nuclear transplantation can be used to clone animals
Animal cloning can be achieved using nuclear transplantation: the nucleus of an egg cell or zygote is replaced with a nucleus from an adult somatic cell.
Using nuclear transplantation to produce new organisms is called reproductive cloning (first used in mammals in 1997 to produce Dolly)
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28. Nuclear transplantation can be used to clone animals
Another way to clone uses embryonic stem (ES) cells harvested from a blastocyst. This procedure can be used to produce
cell cultures for research
stem cells for therapeutic treatments.
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29. Figure 11.13 Nuclear transplantation for cloning
Donor cell
Nucleus from
the donor cell
Reproductive cloning
Blastocyst
The blastocyst is implanted in a surrogate mother.
A clone of the donor is born.
The nucleus is removed from an egg cell.
A somatic cell from an adult donor is added.
The cell grows in culture to produce an early embryo (blastocyst).
Therapeutic cloning
Embryonic stem cells are removed from the blastocyst and grown in culture.
The stem cells are induced to form specialized cells.
Figure Nuclear transplantation for cloning 29

30. The nucleus is removed from an egg cell.
Figure 11.13_1
Donor cell
Nucleus from
the donor cell
Blastocyst
The nucleus is removed from an egg cell.
A somatic cell from an adult donor is added.
The cell grows in culture to produce an early embryo (blastocyst).
Figure 11.13_1 Nuclear transplantation for cloning (part 1) 30

31. The blastocyst is implanted in a surrogate mother.
Figure 11.13_2
Reproductive cloning
Blastocyst
The blastocyst is implanted in a surrogate mother.
A clone of the donor is born.
Therapeutic cloning
Figure 11.13_2 Nuclear transplantation for cloning (part 2)
Embryonic stem cells are removed from the blastocyst and grown in culture.
The stem cells are induced to form specialized cells. 31

32. Reproductive cloning has valuable applications, but human reproductive cloning raises ethical issues
Since Dolly’s landmark birth in 1997, researchers have cloned many other mammals, including mice, cats, horses, cows, mules, pigs, rabbits, ferrets, and dogs.
Cloned animals can show differences in anatomy and behavior due to
environmental influences and
random phenomena.
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33. Reproductive cloning has valuable applications, but human reproductive cloning raises ethical issues
Reproductive cloning is used to produce animals with desirable traits to
produce better agricultural products
produce therapeutic agents
restock populations of endangered animals
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34. Therapeutic cloning can produce stem cells with great medical potential
When grown in laboratory culture, stem cells can
divide indefinitely
give rise to many types of differentiated cells
Adult stem cells can give rise to many, but not all, types of cells
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35. Therapeutic cloning can produce stem cells with great medical potential
Embryonic stem cells are considered more promising than adult stem cells for medical applications.
The ultimate aim of therapeutic cloning is to supply cells for the repair of damaged or diseased organs.
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36. Adult stem cells in bone marrow Cultured embryonic stem cells
Figure 11.15
Blood cells
Adult stem cells in bone marrow
Nerve cells
Cultured embryonic stem cells
Figure Differentiation of stem cells in culture
Heart muscle cells
Different culture conditions
Different types of differentiated cells 36

37. THE GENETIC BASIS OF CANCER
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38. Cancer results from mutations in genes that control cell division
Mutations in two types of genes can cause cancer.
Oncogenes
Proto-oncogenes are normal genes that promote cell division.
Mutations to proto-oncogenes create cancer-causing oncogenes that often stimulate cell division.
Tumor-suppressor genes
Tumor-suppressor genes normally inhibit cell division or function in the repair of DNA damage.
Mutations inactivate the genes and allow uncontrolled division to occur.
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39. Proto-oncogene (for a protein that stimulates cell division)
DNA
A mutation within the gene
Multiple copies of the gene
The gene is moved to a new DNA locus, under new controls
Oncogene
New promoter
Figure 11.16A Alternative ways to make oncogenes from a proto-oncogene (all leading to excessive cell growth)
Hyperactive growth- stimulating protein in a normal amount
Normal growth- stimulating protein in excess
Normal growth- stimulating protein in excess 39

40. Tumor-suppressor gene Mutated tumor-suppressor gene
Normal growth- inhibiting protein
Defective, nonfunctioning protein
Cell division not under control
Cell division under control
Figure 11.16B The effect of a mutation in a tumor-suppressor gene 40

41. An oncogene is activated A tumor-suppressor gene is inactivated
DNA changes:
An oncogene is activated
A tumor-suppressor gene is inactivated
A second tumor- suppressor gene is inactivated
Cellular changes:
Increased cell division
Growth of a polyp
Growth of a malignant tumor 1 2 3
Figure 11.17A Stepwise development of a typical colon cancer
Colon wall 41

42. 1 mutation 2 mutations 3 mutations 4 mutations Chromosomes Normal cell
Figure 11.17B
1 mutation
2 mutations
3 mutations
4 mutations
Chromosomes
Normal cell
Malignant cell
Figure 11.17B Accumulation of mutations in the development of a cancer cell 42

43. Lifestyle choices can reduce the risk of cancer
After heart disease, cancer is the second-leading cause of death in most industrialized nations.
Cancer can run in families if an individual inherits an oncogene or a mutant allele of a tumor-suppressor gene that makes cancer one step closer.
But most cancers cannot be associated with an inherited mutation.
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44. Lifestyle choices can reduce the risk of cancer
Carcinogens are cancer-causing agents that alter DNA.
Most mutagens (substances that promote mutations) are carcinogens.
Two of the most potent carcinogens (mutagens) are
X-rays
ultraviolet radiation in sunlight.
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45. Lifestyle choices can reduce the risk of cancer
The one substance known to cause more cases and types of cancer than any other single agent is tobacco smoke.
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