Regulation of Gene Activity and Gene Mutations Chapter 15 Regulation of Gene Activity and Gene Mutations
15.1 Prokaryotic Regulation Operons regulate genes in prokaryoes operon model proposed by Francois Jacob and Jacques Monad to explain gene regulation in prokaryotes operon: group of structural and regulating genes that function as a single unit
15.1 Prokaryotic Regulation Operons regulate genes in prokaryoes, cont. operon, cont. regulator gene: encodes a protein called repressor that controls the operon parts of an operon: promoter: where RNA polymerase binds to start transcription (signals start of a gene)
The parts of an operon
Parts of an Operon Regulator Gene Promoter Structural Genes Terminator RNA Polymerase Repressor DNA Operator When Repressor is at the operator, RNA Polymerase can’t attach to the Promoter and transcription is blocked
15.1 Prokaryotic Regulation Operons regulate genes in prokaryoes, cont. operon, cont. parts of an operon, cont. operator: where an active repressor binds to prevent transcription by overlapping the promoter (preventing RNA polymerase binding)
15.1 Prokaryotic Regulation Operons regulate genes in prokaryoes, cont. operon, cont. parts of an operon, cont. structural genes: one to several genes coding for enzymes of a metabolic pathway terminator: transcription stop sequence
15.1 Prokaryotic Regulation The trp Operon usually in the “on” position five structural genes code for five enzymes involved in synthesis of amino acid tryptophan the regulator codes for a repressor that ordinarily cannot attach to the operator
15.1 Prokaryotic Regulation The trp Operon, cont. regulation if tryptophan is already present, cell does not need tryptophan-synthesizing enzymes tryptophan binds to repressor, causing a change in shape tryptophan is a corepressor repressor binds to operator therefore trp operon is a repressible operon
Fig. 15.1 The trp operon
Negative feedback of trp metabolism
15.1 Prokaryotic Regulation The lac Operon usually in the “off” position three structural genes code for three enzymes involved in lactose metabolism one breaks lactose into glucose and galactose another allows lactose to enter the cell the regulator codes for a repressor that ordinarily binds to operon
15.1 Prokaryotic Regulation The lac Operon, cont. regulation when lactose is absent, cell does not need lactose-metabolizing enzymes when glucose is absent and lactose is present, lactose binds to the repressor, causing a change in shape lactose is an inducer repressor cannot bind to operator
Fig. 15.2 The lac operon
15.1 Prokaryotic Regulation The lac Operon, cont. regulation, cont. therefore lac operon is an inducible operon cAMP/CAP system when glucose is present, more ATP is available (and less cAMP) when glucose is absent, cyclic AMP (cAMP) accumulates cAMP: derived from ATP; has one phosphate attached in two places
Cyclic AMP
15.1 Prokaryotic Regulation The lac Operon, cont. cAMP/CAP system, cont. cAMP binds to catabolite activator protein (CAP) complex attaches to CAP binding site next to lac promoter DNA bends to better expose promoter to RNA polymerase, increasing the rate of transcription
Fig. 15.3a CAP activity, no glucose
Fig. 15.3b CAP activity, glucose
15.1 Prokaryotic Regulation The lac Operon, cont. cAMP/CAP system, cont. when [lactose] = 0, no transcription when [lactose] = high and ATP:cAMP = high, minimum transcription when [lactose] = high and ATP:cAMP = low, maximum transcription
15.2 Eukaryotic Regulation Eukaryotic DNA differs from prokaryotic DNA in key ways Prokaryotes Eukaryotes circular chromosomes linear chromosomes one chromosome many chromosomes no proteins many proteins not repetitive highly repetitive regulated by operons regulation more complex
Fig. 15.4 Eukaryotic gene regulation
15.2 Eukaryotic Regulation Eukaryotes possess a variety of mechanisms to regulate gene expression Chromatin Structure 1. chromatin consists of DNA (2 nm) wound around histones histones help organize DNA and prevent access to DNA 2. each core of eight histones (and DNA) forms a nucleosome (11 nm)
15.2 Eukaryotic Regulation Chromatin Structure, cont. 3. nucleosomes coil (30 nm) 4. euchromatin: looped chromatin (300 nm) state most chromatin is in 5. heterochromatin: condensed chromatin (700 nm) inactive 6. condensed chromosome (1,400 nm)
Fig. 15.5a Levels of chromatin struct.
Fig. 15.5b Hetero- and euchromatin
Fig. 15.5c A nucleosome
15.2 Eukaryotic Regulation Chromatin Structure, cont. Barr bodies are inactivated X chromosomes in cells of mammalian females do not produce gene products in heterochromatin form X-inactivation is random epigenetic inheritance is the transmission of genetic information outside the coding sequence of a gene
Fig. 15.6 X-inactivation
Fig. 15.6a X-inactivation
Fig. 15.6b Tortoiseshell cat
15.2 Eukaryotic Regulation Transcriptional Control no operons Transcription Factors and Activators transcription factors: proteins that regulate transcription bind to promoter attract and bind RNA polymerase transcription activators: also promote transcription bind to enhancer bridged by mediators
Fig. 15.8 Initiation of transcription
15.2 Eukaryotic Regulation Transcriptional Control, cont. Transposons transposons are DNA sequences that can move within and between chromosomes they usually decrease or shut down gene expression
Fig. 15B,C Indian corn
15.2 Eukaryotic Regulation Posttranscriptional Control mRNA processing introns removed and exons spliced speed with which mRNA leaves the nucleus Translational Control often involves 5’ cap or 3’ poly-A tail Posttranslational Control inc. protein activation or destruction
Fig. 15.9 mRNA processing
Genetic mutations can dramatically affect phenotype Effect of Mutations on Protein Activity point mutation: change in a single DNA nucleotide; could change amino acid frameshift mutation: nucleotides are inserted or deleted from DNA; could change every codon!
Fig. 15.10 Point mutation
Mutations
Effect of Mutations…, cont. 15.3 Genetic Mutations Effect of Mutations…, cont. faulty or nonfunctional proteins can have a dramatic effect on phenotype examples: hemophilia phenylketonuria albinism cystic fibrosis androgen insensitivity syndrome
15.3 Genetic Mutations Carcinogenesis tumor suppressor genes and proto-oncogenes often code for transcription factors or proteins that control transcription factors example: p53 (tumor suppressor gene) is often mutated in human cancers; p53 is a transcription factor often involved in turning on genes that produce cell cycle inhibitors
Fig. 15.12 Carcinogenesis
15.3 Genetic Mutations Causes of Mutations spontaneous spontaneous mutations due to DNA replication errors are rare environmental mutagens increase the chances of a mutation carcinogens are mutagens that cause cancer chemicals, smoke, X-rays, gamma rays, UV light
Fig. 15.13 Results of mutations
Result of UV radiation exposure