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Regulation of a metabolic pathway
- tryptophan can both
- (a) inhibit the activity of the first enzyme in the pathway (feedback inhibition)
- (b) Regulation of gene expression/ enzyme production
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operator
- The switch is a segment of DNA
- controls the access of RNA polymerase to the genes
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operon ( Prokaryotic/ Bacteria)
entire stretch of DNA required for enzyme production for the tryptophan pathway
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trp operon in E. coli (repressive)
- Genes: TrpE -> TrpA
- Tryptophan present, repressor active, operator off/ operon off
- anabolic
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repressor
turn on operator, preventing transcription of the genes
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corepressor
- asmall molecule that cooperates with a repressor protein to switch an operon off
- Ex. Tryptophan
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lac operon (Inducible)
- lacZ, lacY, lacA
- lac repressor,in contrast, is active by itself
- inducer(allolactose), inactivates the repressor
- Lactose present, repressor inactive, operon on.
- Lactorse-> remove repressor -> operon ON!
- catabolic
- neg control by repressor, positive by CAP
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cyclic AMP (cAMP)
- when glucose is scarce-> cAMP is high -> active ap -> increases the affinity of RNA polymerase
- activator (cap) a protein that binds to DNA and stimulates transcriptionof a gene.
- when glucose present/ cAMP is low -> little lac mRNA synthesized
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differential gene expression (Eu.)
the expression of different genes by cells with the same genome
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Regulation of Chromatin Structure
- The location of agene’s promoter ror nuclear laminacan affect whether the gene is transcribed
- chemical modifications tothe histone proteins and to the DNA of chromatin can influence both chromatin structure and gene expression.
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effect of histone acetylation
- Histone tails protrude outward from a nucleosome/ accessible for chemical modification
- Acetylation of histone tails promotes loose chromatin structure that permits transcription
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DNA methylation
- addition of methyl groups to certain bases
- inactivation of genes/alleles
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epigenetic inheritance
Inheritance of traits transmitted by mechanisms not directly involving the nucleotidesequence
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control elements
segments of noncoding DNA that serve as binding sites for the proteins called transcription factors,which in turn regulate transcription
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Enhancers
- distal control elements
- rate of gene expression can be increased or decreased by binding specifice transcription factors, activators/ repressors
- Bending of the DNA by a protein enables enhancers to influence a promoter
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Protein-mediated bending of
bring the bound activators into contact with a group of mediator proteins, which in turn interact with proteins at the promoter.
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Chromosomal interactions in the interphase nucleus.
Although each chromosome has its own territory loops of chromatin may extend into othersites in the nucleus.
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RNA-processing
alternative RNA splicing, different mRNA molecules are produced from the same primary transcript, dependingo n which RNA segments are treated as exons and which as introns.
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ubiquitin
- cell commonly attaches moleculesof a small protein(ubiquitin) to proten for destruction
- recognize by proteasome -> fragments(petides)
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•Mechanisms:
- Alternative mRNA splicing
- mRNAdegradation
- Translation initiation
- Protein degradation
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Noncoding RNAs
- Only a small fraction of DNA codes for proteins
- RNA interference: The process of inhibiting gene expression using RNA molecules
- - MicroRNAs: small single-stranded RNA molecules that can bind to mRNA
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oncogenes
- cancer-causing genes
- found in the genomes of humans and other animals
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proto-oncogenes
code for proteins that stimulate normal cell growth and division
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proto-oncogenes to oncogenes
- movement of DNA within the genome
- amplification of a proto-oncogene
- point mutations in a control element or in the proto-oncogene itself (promoter or enhancer, the coding sequence
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tumor-suppressor genes
- proteins they encode help prevent uncontrolled cell growth.
- repair damaged DNA,
- control the adhesion of cells to each other or to the extracellula rmatrix
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ras gene
- G protein that relays a signal from a growth factor receptor on the plasma membrane to a cascade of protein kinases
- lead to production of a hyperactive Ras protein that triggers the kinase cascade -> increased cell division/ excessive cell growth
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p53 gene
- tumor suppressor gene
- prevents a cell from assing on mutations due to DNA damage – it halts the cell cycle
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Cancer developement
- Multiple mutations are generally needed for
- full-fledged cancer; thus the incidence increases with age
- individuals can inherit oncogenes or mutant alleles of tumor-suppressor genes
- Example: Breast Cancer - BRCA1 & BRAC2 genes
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