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PowerLecture:PowerLecture:Chapter 15Chapter 15
Controls over GenesControls over Genes
Loss of gene controls can be disastrousLoss of gene controls can be disastrous
Some gene mutations, either inherited or spontaneously Some gene mutations, either inherited or spontaneously mutated due to environmental factors, predispose mutated due to environmental factors, predispose individuals to develop cancerindividuals to develop cancer
ERBB2, a type of membrane receptor, is encoded on ERBB2, a type of membrane receptor, is encoded on chromosome 17chromosome 17
This gene controls the cell cycle - overexpression or This gene controls the cell cycle - overexpression or mutation triggers cancerous transformationsmutation triggers cancerous transformations
Impacts, Issues: Impacts, Issues: Between You Between You and Eternityand Eternity
BRCA1 and BRCA2 are tumor BRCA1 and BRCA2 are tumor suppressing proteins that fix damaged suppressing proteins that fix damaged DNADNA
Breast cancer cells often contain their Breast cancer cells often contain their mutated formsmutated forms
Impacts, Issues: Impacts, Issues: Between You Between You and Eternityand Eternity
Changes in DNA Changes in DNA Trigger CancerTrigger Cancer
Ultraviolet Ultraviolet
radiation can radiation can
cause breakscause breaks
Can promote Can promote
formation of formation of
dimersdimers
Controlling the Cell CycleControlling the Cell Cycle
Cycle has built-in checkpointsCycle has built-in checkpoints Proteins monitor chromosome structure, Proteins monitor chromosome structure,
whether conditions favor division, etc.whether conditions favor division, etc. Proteins are products of checkpoint genesProteins are products of checkpoint genes KinasesKinases Growth factors Growth factors
OncogenesOncogenes
Have potential to induce cancerHave potential to induce cancer
Mutated forms of normal genesMutated forms of normal genes
Can form following insertions of viral Can form following insertions of viral
DNA into DNA or after carcinogens DNA into DNA or after carcinogens
change the DNAchange the DNA
Cancer CharacteristicsCancer Characteristics
Plasma membrane and cytoplasm Plasma membrane and cytoplasm
alteredaltered
Cells grow and divide abnormallyCells grow and divide abnormally
Weakened capacity for adhesionWeakened capacity for adhesion
Lethal unless eradicatedLethal unless eradicated
ApoptosisApoptosis
Programmed cell deathProgrammed cell death
Signals unleash molecular weapons of Signals unleash molecular weapons of
self-destructionself-destruction
Cancer cells do not commit suicide on cue Cancer cells do not commit suicide on cue
Gene ControlGene Control
Which genes are expressed in a cell Which genes are expressed in a cell depends upon:depends upon:
• • Type of cellType of cell
• • Internal chemical conditionsInternal chemical conditions
• • External signalsExternal signals
• • Built-in control systemsBuilt-in control systems
Mechanisms of Gene ControlMechanisms of Gene Control
Controls related to transcriptionControls related to transcription
Transcript-processing controlsTranscript-processing controls
Controls over translationControls over translation
Post-translation controlsPost-translation controls
Regulatory ProteinsRegulatory Proteins
Can exert control over gene Can exert control over gene
expression through interactions with:expression through interactions with:
DNADNA
RNARNA
New polypeptide chainsNew polypeptide chains
Final proteinsFinal proteins
Control MechanismsControl Mechanisms
Negative controlNegative control Regulatory proteins slow down Regulatory proteins slow down
or curtail gene activity or curtail gene activity
Positive controlPositive control
Regulatory proteins promote or Regulatory proteins promote or
enhance gene activitiesenhance gene activities
Control MechanismsControl Mechanisms
PromotersPromoters
EnhancersEnhancers
Chemical ModificationsChemical Modifications
Methylation of DNA Methylation of DNA can inactivate can inactivate genesgenes
Acetylation of Acetylation of histones allows histones allows DNA unpacking DNA unpacking and transcriptionand transcription
Controls in Eukaryotic CellsControls in Eukaryotic Cells
Control of transcriptionControl of transcription
Transcript processing controlsTranscript processing controls
Controls over translationControls over translation
Controls following translationControls following translation
DNApre-mRNAtranscript
mRNA
NUCLEUS
mRNA
CTYOPLASMtranslational
controlproteinproduct
proteinproductcontrol
inactivatedprotein
inactivatedmRNA
mRNAdegradation
control
mRNAtransportcontrol
transportprocessing
control
transcriptioncontrol
Fig. 15-3, p.233
Controls in Eukaryotic Cells
Chromosome PuffChromosome Puff
Portion of the Portion of the
chromosome in which the chromosome in which the
DNA has loosened up to DNA has loosened up to
allow transcriptionallow transcription
Translation of transcripts Translation of transcripts
from puffed region from puffed region
produces protein produces protein
components of salivacomponents of saliva
X Chromosome InactivationX Chromosome Inactivation
One X inactivated in each cell of femaleOne X inactivated in each cell of female
Creates a “mosaic” for X chromosomesCreates a “mosaic” for X chromosomes
Governed by Governed by XISTXIST gene gene
A condensed X A condensed X chromosome (Barr chromosome (Barr body) in the somatic body) in the somatic cell nucleus of a cell nucleus of a human femalehuman female
Fig. 15-4a, p.234
X Chromosome InactivationX Chromosome Inactivation
Most Genes Are Turned OffMost Genes Are Turned Off
Cells of a multicelled organism rarely Cells of a multicelled organism rarely use more than 5-10 percent of their use more than 5-10 percent of their genes at any given timegenes at any given time
The remaining genes are selectively The remaining genes are selectively expressedexpressed
PhytochromePhytochrome
Signaling molecule in plantsSignaling molecule in plants
Activated by red wavelengths, Activated by red wavelengths, inactivated by far-red wavelengthsinactivated by far-red wavelengths
Changes in phytochrome activity Changes in phytochrome activity influence transcription of certain genesinfluence transcription of certain genes
Fig. 15-6, p.235
petal
carpel
sepal
stamen
Fig. 15-6, p.235
B
A C
1 2 3 4
petals carpel
sepals stamens
Fig. 15-6, p.235
Fig. 15-6, p.235
Fig. 15-6, p.235
Fig. 15-6, p.235
Fig. 15-6, p.235
Homeotic GenesHomeotic Genes
Occur in all eukaryotesOccur in all eukaryotes Master genes that control development of Master genes that control development of
body partsbody parts Encode homeodomains (regulatory Encode homeodomains (regulatory
proteins)proteins) Homeobox sequence can bind to Homeobox sequence can bind to
promoters and enhancerspromoters and enhancers
Knockout ExperimentsKnockout Experiments
Prevent a gene’s transcription or translationPrevent a gene’s transcription or translation Differences between genetically engineered Differences between genetically engineered
knockout individuals and wild-type individuals knockout individuals and wild-type individuals point to function of knocked out genepoint to function of knocked out gene
Knockout experiments shed light on genes that Knockout experiments shed light on genes that function in function in DrosophilaDrosophila development development
Fig. 15-7c, p.237
Knockout ExperimentsKnockout Experiments
Fig. 15-8a, p.237
A7 A5 A3 A1 T2A8
A8
A4 A2 T3 T1T2 T2
T2
A7A6A5A4
A3
A2
A1T3 T2 T1 Lb
Mx Md
A8
A7
A6
A5
A4 A3 A2 A1 T3T2
T1
A8A7A6
A4A3 A2
A1 T3 T2T1
Body Plan
Fig. 15-8b, p.237
Body Plan
Fig. 15-8c, p.237
Body Plan
Gene Control in ProkaryotesGene Control in Prokaryotes
No nucleus separates DNA from No nucleus separates DNA from
ribosomes in cytoplasmribosomes in cytoplasm
When nutrient supply is high, When nutrient supply is high,
transcription is fasttranscription is fast
Translation occurs even before Translation occurs even before
mRNA transcripts are finishedmRNA transcripts are finished
The The Lactose Operon
gene 1 gene 2 gene 3
lactose operon
regulatory gene
transcription,translation
operator
operator
promoter
repressor protein
Fig.15-10, p. 241
High LactoseHigh Lactose
gene 1operator operatorpromoter
mRNA RNA polymerase
lactose
allolactose
Fig.15-10, p. 241
Low LactoseLow Lactose
Repressor binds to operatorRepressor binds to operator
Binding blocks promoterBinding blocks promoter
Transcription is blockedTranscription is blocked
Fig.15-10, p. 241
CAP Exerts Positive ControlCAP Exerts Positive Control
CAP is an activator protein CAP is an activator protein
Adheres to promoter only when in Adheres to promoter only when in
complex with cAMP complex with cAMP
Level of cAMP depends on level of Level of cAMP depends on level of
glucoseglucose
Positive Control – Positive Control – High GlucoseHigh Glucose
There is little cAMPThere is little cAMP
CAP cannot be activatedCAP cannot be activated
The promoter is not good at binding The promoter is not good at binding
RNA polymeraseRNA polymerase
The lactose-metabolizing genes are The lactose-metabolizing genes are
not transcribed very muchnot transcribed very much
Positive Control – Positive Control – Low GlucoseLow Glucose
cAMP accumulatescAMP accumulates
CAP-cAMP complex formsCAP-cAMP complex forms
Complex binds to promoterComplex binds to promoter
RNA polymerase can now bindRNA polymerase can now bind
The lactose-metabolizing genes are The lactose-metabolizing genes are
transcribed rapidlytranscribed rapidly
HormonesHormones
Signaling moleculesSignaling molecules Stimulate or inhibit activity in target cellsStimulate or inhibit activity in target cells Mechanism of action variesMechanism of action varies
May bind to cell surfaceMay bind to cell surface May enter cell and bind to regulatory May enter cell and bind to regulatory
proteinsproteins May bind with enhancers in DNAMay bind with enhancers in DNA
Polytene ChromosomesPolytene Chromosomes
Occur in salivary Occur in salivary glands of midge glands of midge larvae larvae
Consist of multiple Consist of multiple DNA moleculesDNA molecules
Can produce Can produce multiple copies of multiple copies of transcripts transcripts
Vertebrate HormonesVertebrate Hormones
Some have widespread effectsSome have widespread effects
Somatotropin (growth hormone)Somatotropin (growth hormone)
Others signal only certain cells at Others signal only certain cells at
certain timescertain times
Prolactin stimulates milk Prolactin stimulates milk
production production
Fig. 15-11a, p.241
Fig. 15-11b, p.241