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Fig. 18-1. Precursor. Feedback inhibition. trpE gene. Fig. 18-2. Enzyme 1. trpD gene. Regulation of gene expression. trpC gene. Enzyme 2. trpB gene. Enzyme 3. trpA gene. Tryptophan. (a) Regulation of enzyme activity. (b) Regulation of enzyme production. trp operon.
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Precursor Feedback inhibition trpE gene Fig. 18-2 Enzyme 1 trpD gene Regulation of gene expression trpC gene Enzyme 2 trpB gene Enzyme 3 trpA gene Tryptophan (a) Regulation of enzyme activity (b) Regulation of enzyme production
trp operon Promoter Promoter Genes of operon DNA trpD trpB trpA trpE trpC trpR Fig. 18-3 Operator Regulatory gene Stop codon Start codon 3 mRNA 5 RNA polymerase mRNA 5 D E C B A Protein Inactive repressor Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on DNA No RNA made mRNA Protein Active repressor Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off
Fig. 18-3a trp operon Promoter Promoter Genes of operon DNA trpD trpR trpE trpC trpB trpA Operator Regulatory gene Stop codon Start codon 3 mRNA 5 RNA polymerase mRNA 5 B A D C E Protein Inactive repressor Polypeptide subunits that make up enzymes for tryptophan synthesis (a) Tryptophan absent, repressor inactive, operon on
Fig. 18-3b-1 DNA No RNA made mRNA Protein Active repressor Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off
Fig. 18-3b-2 DNA No RNA made mRNA Protein Active repressor Tryptophan (corepressor) (b) Tryptophan present, repressor active, operon off
Regulatory gene Promoter Operator lacZ lacI DNA No RNA made Fig. 18-4 3 mRNA RNA polymerase 5 Active repressor Protein (a) Lactose absent, repressor active, operon off lac operon lacZ DNA lacI lacY lacA RNA polymerase 3 mRNA mRNA 5 5 Permease -Galactosidase Transacetylase Protein Inactive repressor Allolactose (inducer) (b) Lactose present, repressor inactive, operon on
Regulatory gene Promoter Operator Fig. 18-4a lacI lacZ DNA No RNA made 3 mRNA RNA polymerase 5 Active repressor Protein (a) Lactose absent, repressor active, operon off
Fig. 18-4b lac operon lacY DNA lacI lacZ lacA RNA polymerase 3 mRNA mRNA 5 5 Permease Transacetylase -Galactosidase Protein Inactive repressor Allolactose (inducer) (b) Lactose present, repressor inactive, operon on
Promoter Operator DNA lacI lacZ Fig. 18-5 RNA polymerase binds and transcribes CAP-binding site Active CAP cAMP Inactive lac repressor Inactive CAP Allolactose (a) Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized Promoter Operator DNA lacI lacZ CAP-binding site RNA polymerase less likely to bind Inactive CAP Inactive lac repressor (b) Lactose present, glucose present (cAMP level low): little lac mRNA synthesized
Signal NUCLEUS Chromatin Chromatin modification Fig. 18-6 DNA Gene available for transcription Gene Transcription RNA Exon Primary transcript Intron RNA processing Tail mRNA in nucleus Cap Transport to cytoplasm CYTOPLASM mRNA in cytoplasm Translation Degradation of mRNA Polypeptide Protein processing Active protein Degradation of protein Transport to cellular destination Cellular function
Signal NUCLEUS Fig. 18-6a Chromatin Chromatin modification DNA Gene available for transcription Gene Transcription Exon RNA Primary transcript Intron RNA processing Tail mRNA in nucleus Cap Transport to cytoplasm CYTOPLASM
CYTOPLASM mRNA in cytoplasm Fig. 18-6b Translation Degradation of mRNA Polypeptide Protein processing Active protein Degradation of protein Transport to cellular destination Cellular function
Fig. 18-7 Histone tails Amino acids available for chemical modification DNA double helix (a) Histone tails protrude outward from a nucleosome Unacetylated histones Acetylated histones (b) Acetylation of histone tails promotes loose chromatin structure that permits transcription
Fig. 18-8-1 Poly-A signal sequence Enhancer (distal control elements) Proximal control elements Termination region Exon Intron Exon Intron Exon DNA Upstream Downstream Promoter
Fig. 18-8-2 Poly-A signal sequence Enhancer (distal control elements) Proximal control elements Termination region Exon Intron Exon Intron Exon DNA Upstream Downstream Promoter Transcription Exon Intron Exon Intron Exon Primary RNA transcript Cleaved 3 end of primary transcript 5 Poly-A signal
Fig. 18-8-3 Poly-A signal sequence Enhancer (distal control elements) Proximal control elements Termination region Exon Intron Exon Intron Exon DNA Upstream Downstream Promoter Transcription Exon Intron Exon Intron Exon Primary RNA transcript Cleaved 3 end of primary transcript 5 RNA processing Intron RNA Poly-A signal Coding segment mRNA 3 Start codon Stop codon Poly-A tail 3 UTR 5 Cap 5 UTR
Promoter Activators Gene DNA Distal control element Enhancer TATA box Fig. 18-9-1
Promoter Activators Gene DNA Distal control element Enhancer TATA box Fig. 18-9-2 General transcription factors DNA-bending protein Group of mediator proteins
Promoter Activators Gene DNA Distal control element Enhancer TATA box Fig. 18-9-3 General transcription factors DNA-bending protein Group of mediator proteins RNA polymerase II RNA polymerase II Transcription initiation complex RNA synthesis
Enhancer Promoter Albumin gene Control elements Fig. 18-10 Crystallin gene LIVER CELL NUCLEUS LENS CELL NUCLEUS Available activators Available activators Albumin gene not expressed Albumin gene expressed Crystallin gene not expressed Crystallin gene expressed (a) Liver cell (b) Lens cell
Exons Fig. 18-11 DNA Troponin T gene Primary RNA transcript RNA splicing or mRNA
Fig. 18-12 Proteasome and ubiquitin to be recycled Ubiquitin Proteasome Ubiquitinated protein Protein to be degraded Protein fragments (peptides) Protein entering a proteasome
Hairpin miRNA Hydrogen bond Fig. 18-13 Dicer miRNA miRNA- protein complex 5 3 (a) Primary miRNA transcript mRNA degraded Translation blocked (b) Generation and function of miRNAs
Fig. 18-14 (a) Fertilized eggs of a frog (b) Newly hatched tadpole
Fig. 18-14a (a) Fertilized eggs of a frog
Fig. 18-14b (b) Newly hatched tadpole
Fig. 18-15 Unfertilized egg cell Sperm Nucleus Fertilization Two different cytoplasmic determinants NUCLEUS Early embryo (32 cells) Zygote Signal transduction pathway Mitotic cell division Signal receptor Signal molecule (inducer) Two-celled embryo (b) Induction by nearby cells (a) Cytoplasmic determinants in the egg
Unfertilized egg cell Sperm Nucleus Fig. 18-15a Fertilization Two different cytoplasmic determinants Zygote Mitotic cell division Two-celled embryo (a) Cytoplasmic determinants in the egg
Fig. 18-15b NUCLEUS Early embryo (32 cells) Signal transduction pathway Signal receptor Signal molecule (inducer) (b) Induction by nearby cells
Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell Fig. 18-16-1 OFF OFF
Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell Fig. 18-16-2 OFF OFF OFF mRNA MyoD protein (transcription factor) Myoblast (determined)
Nucleus Master regulatory gene myoD Other muscle-specific genes DNA Embryonic precursor cell Fig. 18-16-3 OFF OFF OFF mRNA MyoD protein (transcription factor) Myoblast (determined) mRNA mRNA mRNA mRNA Myosin, other muscle proteins, and cell cycle– blocking proteins MyoD Another transcription factor Part of a muscle fiber (fully differentiated cell)
Thorax Head Abdomen 0.5 mm Dorsal Fig. 18-17 Right BODY AXES Anterior Posterior Left Ventral (a) Adult Follicle cell Egg cell developing within ovarian follicle 1 Nucleus Egg cell Nurse cell Egg shell Unfertilized egg 2 Depleted nurse cells Fertilization Laying of egg Fertilized egg 3 Embryonic development Segmented embryo 4 0.1 mm Body segments Hatching Larval stage 5 (b) Development from egg to larva
Thorax Head Abdomen Fig. 18-17a 0.5 mm Dorsal Right BODY AXES Posterior Anterior Left Ventral (a) Adult
Follicle cell Egg cell developing within ovarian follicle 1 Nucleus Egg cell Fig. 18-17b Nurse cell Egg shell Unfertilized egg 2 Depleted nurse cells Fertilization Laying of egg Fertilized egg 3 Embryonic development Segmented embryo 4 0.1 mm Body segments Hatching Larval stage 5 (b) Development from egg to larva
Fig. 18-18 Eye Leg Antenna Wild type Mutant
Fig. 18-18a Eye Antenna Wild type
Fig. 18-18b Leg Mutant
EXPERIMENT Tail Head Fig. 18-19 A8 T1 T2 A7 T3 A6 A1 A5 A2 A3 A4 Wild-type larva Tail Tail A8 A8 A7 A7 A6 Mutant larva (bicoid) RESULTS Fertilization, translation of bicoid mRNA Anterior end 100 µm Bicoid mRNA in mature unfertilized egg Bicoid protein in early embryo CONCLUSION Nurse cells Egg bicoid mRNA Bicoid mRNA in mature unfertilized egg Bicoid protein in early embryo Developing egg
EXPERIMENT Tail Fig. 18-19a Head A8 T1 T2 A7 T3 A6 A1 A5 A2 A3 A4 Wild-type larva Tail Tail A8 A8 A7 A7 A6 Mutant larva (bicoid)
Fig. 18-19b RESULTS Fertilization, translation of bicoid mRNA Anterior end 100 µm Bicoid mRNA in mature unfertilized egg Bicoid protein in early embryo
Fig. 18-19c CONCLUSION Nurse cells Egg bicoid mRNA Bicoid mRNA in mature unfertilized egg Developing egg Bicoid protein in early embryo
Fig. 18-20 Proto-oncogene DNA Point mutation: Gene amplification: Translocation or transposition: within the gene within a control element New promoter Oncogene Oncogene Normal growth- stimulating protein in excess Normal growth-stimulating protein in excess Normal growth- stimulating protein in excess Hyperactive or degradation- resistant protein
Growth factor 1 MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Ras G protein 3 GTP Ras GTP Fig. 18-21 2 4 Protein kinases (phosphorylation cascade) Receptor NUCLEUS Transcription factor (activator) 5 DNA Gene expression Protein that stimulates the cell cycle (a) Cell cycle–stimulating pathway 2 Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription Active form of p53 3 UV light 1 DNA damage in genome DNA Protein that inhibits the cell cycle (b) Cell cycle–inhibiting pathway EFFECTS OF MUTATIONS Protein overexpressed Protein absent Cell cycle overstimulated Cell cycle not inhibited Increased cell division (c) Effects of mutations
1 1 Growth factor MUTATION Hyperactive Ras protein (product of oncogene) issues signals on its own Ras G protein 3 GTP Fig. 18-21a Ras GTP 2 Protein kinases (phosphorylation cascade) Receptor 4 NUCLEUS Transcription factor (activator) 5 DNA Gene expression Protein that stimulates the cell cycle (a) Cell cycle–stimulating pathway
Fig. 18-21b 2 Protein kinases MUTATION Defective or missing transcription factor, such as p53, cannot activate transcription 3 Active form of p53 UV light 1 DNA damage in genome DNA Protein that inhibits the cell cycle (b) Cell cycle–inhibiting pathway
Fig. 18-21c EFFECTS OF MUTATIONS Protein overexpressed Protein absent Cell cycle overstimulated Cell cycle not inhibited Increased cell division (c) Effects of mutations
Fig. 18-22 Colon EFFECTS OF MUTATIONS Loss of tumor-suppressor gene p53 4 1 Loss of tumor- suppressor gene APC (or other) Activation of ras oncogene 2 Colon wall Loss of tumor-suppressor gene DCC 3 Additional mutations 5 Normal colon epithelial cells Small benign growth (polyp) Larger benign growth (adenoma) Malignant tumor (carcinoma)
Colon Fig. 18-22a Colon wall Normal colon epithelial cells