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