Gene Regulation 2
Outline
Prokaryotic Regulation trp Operon lac Operon
Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control
Genetic Mutations Cancer
Gene Regulation 3Prokaryotic Regulation:
The Operon Model
Operon consist of three componentsPromoterDNA sequence where RNA polymerase first attaches Short segment of DNA
OperatorDNA sequence where active repressor binds Short segment of DNA
Structural GenesOne to several genes coding for enzymes of a metabolic pathway Translated simultaneously as a block Long segment of DNA
Gene Regulation 4Repressible Operons:
The trp Operon
The regulator codes for a repressor
If tryptophan (an amino acid) is absent:
Repressor is unable to attach to the operator (expression is normally “on”)
RNA polymerase binds to the promoter
Enzymes for synthesis of tryptophan are produced
If tryptophan is present:
Combines with repressor as corepressor
Repressor becomes functional
Blocks synthesis of enzymes and tryptophan
Gene Regulation 6Inducible Operons:
The lac Operon
The regulator codes for a repressor
If lactose (a sugar that can be used for food) is absent: Repressor attaches to the operator Expression is normally “off”
If lactose is present: It combines with repressor and renders it unable to bind to operator
RNA polymerase binds to the promoter The three enzymes necessary for lactose catabolism are produced
Gene Regulation 9
Eukaryotic Regulation
A variety of mechanisms
Five primary levels of control:Nuclear levels Chromatin Packing
Transcriptional Control
Posttranscriptional Control
Cytoplasmic levels Translational Control
Posttranslational Control
Gene Regulation 11
Chromatin Structure
Eukaryotic DNA associated with histone proteins Together make up chromatinAs seen in the interphase nucleus
Nucleosomes:DNA wound around balls of eight molecules of histone proteins
Looks like beads on a stringEach bead a nucleosome
The levels of chromatin packing determined by degree of nucleosome coiling
Gene Regulation 13
Chromatin Packing
Euchromatin Loosely coiled DNA Transcriptionally active
Heterochromatin Tightly packed DNA Transcriptionally inactive
Barr Bodies Females have two X chromosomes, but only one is active
Other is tightly packed along its entire length Inactive X chromosome is Barr body
Gene Regulation 15
Transcriptional Control
Transcription controlled by proteins called transcription factors
Bind to enhancer DNA
Regions of DNA where factors that regulate transcription can also bind
Always present in cell, but most likely have to be activated before they will bind to DNA
Gene Regulation 18
Posttranscriptional Control
Posttranscriptional control operates on primary mRNA transcript
Given a specific primary transcript: Excision of introns can vary Splicing of exons can vary Determines the type of mature transcript that leaves the nucleus
May also control speed of mRNA transport from nucleus to cytoplasm Will affect the number of transcripts arriving at rough ER
And therefore the amount of gene product realized per unit time
Gene Regulation 20
Translational Control
Translational Control - Determines degree to which mRNA is translated into a protein productPresence of 5′ cap
Length of poly-A tail on 3′ end
Posttranslational Control - Affects the activity of a protein productActivation
Degradation rate
Gene Regulation 21Effect of Mutations on
Protein Activity
Point Mutations Involve change in a single DNA nucleotide Changes one codon to a different codon Affects on protein vary: Nonfunctional Reduced functionality Unaffected
Frameshift Mutations One or two nucleotides are either inserted or deleted from DNA
Protein always rendered nonfunctional Normal : THE CAT ATE THE RAT After deletion: THE ATA TET HER AT After insertion: THE CCA TAT ETH ERA T
Gene Regulation 24
Carcinogenesis
Development of cancer involves a series of mutations
Proto-oncogenes – Stimulate cell cycle
Tumor suppressor genes – inhibit cell cycle
Mutation in oncogene and tumor suppressor gene:
Stimulates cell cycle uncontrollably
Leads to tumor formation
Gene Regulation 27
Causes of Mutations
Replication Errors1 in 1,000,000,000 replicationsDNA polymerase Proofreads new strandsGenerally corrects errors
Environmental MutagensCarcinogens - Mutagens that increase the chances of cancerUltraviolet Radiation Tobacco Smoke
Gene Regulation 28
Review
Prokaryotic Regulation trp Operon lac Operon
Eukaryotic Regulation Transcriptional Control Posttranscriptional Control Translational Control Posttranslational Control
Genetic Mutations Cancer