Module 6.1.1- Cellular control

• Mutation


  a random change to the sequence of bases in the genetic material
• Mutagens


  A chemical or physical agent that interacts with DNA and causes a mutation.

  
• Point mutation


  gene mutation in which a single base pair in DNA has been changed through substitution of another base
• Frame shift


  genetic mutation caused by a deletion or insertion in a DNA sequence that shifts the way the sequence is read
• Silent point mutation


  A single-base substitution in which there is no change in amino acid since the codon still codes for the same amino acid (degenerate)

  
• Missense point mutation


  The mutation changes the amino acid coded for Therefore could form a different polypeptide chain which different bonds in the tertiary structure

  e.g. sickle cell anaemia

  
• Nonsense point mutation


  The mutation changes from coding for an amino acid to coding for a stop codon

  Shortens the polypeptide chain

  e.g. Duchenne muscular dystrophy

  
• What are the 2 types of frameshift mutations

  insertion and deletion
• Insertion/Deletion frame shift mutation


  a mutation in which one or more nucleotides are added or removed to a gene shifting the reading frame of DNA. Since it is not in multiples of 3s, subsequent base triplets are altered

  e.g. Thalassaemia

  
• Damaging mutations


  proteins are no longer synthesised or the proteins synthesised are non-functional. this could interfere with one or more essential processes.
• Beneficial mutations


  enhance the survival or reproductive success of an organism

  
  

  e.g. the ability to digest lactose
• Chromosome mutations (4 ways)

  Deletion- section of chromosome breaks

  Duplication- sections duplicated on chromosomes

  Translocation- section of 1 chromosome breaks off and joins non-homologous chromosome

  Inversion- section of chromosome breaks off, is reversed and then joined back onto chromosome
• Why is it likely that mutations on chromosomes specifically will not affect the phenotype of the organism


  Chromosomes have telomeres on the edges which are non-coding regions so if mutations occur here, it will not affect the phenotype

  
• Gene regulation


  ability of an organism to control which genes are transcribed in response to the environment

  
  

  can prevent vital resources from being wasted
• 4 types of gene regulation


  -transcriptional (genes turned on and off)

  -post-transcriptional (mRNA can be modified to regulate translation & proteins produced)

  -translational (can be stopped or started)

  -post-translational (proteins can be modified after synthesis to change function)
• DNA (in chromatin remodeling)


  DNA (negatively charged) is wound around proteins called histones(positively charged)in eukaryotic cells to be packed into the nucleus of a cell and this is chromatin
• RNA polymerase


  enzyme that links together the growing chain of RNA nucleotides during transcription using a DNA strand as a template

  
• Heterochromatin


  tightly wound DNA causing chromosomes to be visible during cell division generally not transcribed because RNA polymerase cannot access the genes
• Euchromatin


  loosely wound DNA present during interphase genes freely transcribed since RNA polymerase is able to bind
• What group(s) can you add to

  decrease the degree of packing in histones and why Acetyl(acetylation) or phosphate groups (phosphorylation)

  reduces the positive charge on histones making the DNA coil less tightly
• What group(s) can you add to

  increase the degree of packing in histones and why Methyl(methylation)

  makes histones more hydrophobic so they bind more tightly to each other causing DNA to coil more tightly
• Lac operon


  a gene system whose operator gene and three structural genes lacZ, lacY and lacA control lactose metabolism in E. coli (prokaryotes)

  
• Regulatory gene


  lacI(lac operon) A gene that codes for a protein, such as are pressor, that controls the transcription of another gene or group of genes.
• Repressor protein (lac operon)


  a regulatory protein that binds to the operator region (lacO)and blocks transcription of the genes of an operon
• Promoter region (lac operon)


  site where RNA polymerase binds and initiates transcription
• When lactose is not present (lac operon)

  -the repressor protein, which is continually synthesised under the direction of the Regulatory Gene, binds to the operator region-prevents RNA Polymerase from binding to promoter-there unable to transcribe the structural Genes.
• When lactose is present (lac operon)

  -lactose binds to repressor protein causing it to change shape so it can no longer bind to the operator region

  -RNA polymerase binds to promoter region

  -3 structural genes are transcribed and enzymes are synthesised

  
• What is the function of lactose permease and B-galactosidase lactose permease

  
  

  - makes the bacterial cell more permeable so lactose can enter

  B-galactosidase

  - hydrolyses lactose -> glucose + galactose
• Post-transcriptional regulation


  Control of gene expression after transcription has occured
• Introns and exons

  Introns are non-coding regions of DNA whilst

  Exons are the coding regions
• Splicing


  mature mRNA from pre-mRNA (Post transcriptional process)-mRNA introns are removed and remaining mRNA exons are joined together by endonuclease enzymes.

  • G cap(modified nucleotide) is added to the 5' end-tail
  • (long chain of adenine nucleotides) is added to the 3' end

  both stabilise mRNA and delay degradation in cytoplasm. cap also aids binding of mRNA to ribosomes
• How do you further increase the rate of transcription of enzymes that hydrolyse lactose so it can be used as a respiratory substrate?

  
  

  CRP binds with cAMP to form acAMP receptor protein

  the cAMP receptor protein binds to the promoter region where the RNA polymerase is also bound

  therefore this increases the rate of transcription (due to the activation of protein kinases etc.)
• Why is the protein produced is dependent on how the pre-mRNA is spliced (Post-transcriptional gene regulation)

  Some genes are spliced in different ways and according to how it is spliced they can encode more than one protein (due to different combinations of introns and exons)

  
• Why are a cap and a tail added in forming mature mRNA (5' and 3' end respectively)?

  both cap and tail is added to stabilise mRNA and delay degradation in cytoplasm

  cap also aids binding of mRNA to ribosomes
• Translational control


  -degradation of mRNA: more resistant, the longer it will last in cytoplasm, synthesising more protein

  -binding of inhibitory proteins to mRNA to stop it binding to ribosomes and synthesising proteins

  -activation of initiation factors which aid the binding of mRNA to ribosomes
• Protein kinases


  catalyse the addition of phosphate groups to proteins changing its tertiary structure and thus its function (phosphorylation)

  
• Post-translational control


  Regulation of gene expression by modification of proteins (e.g. addition of a phosphate group or sugar residues)after translation.
• 4 ways to modify a protein (Post-translation control)

  -addition of non-protein group e.g. carbohydrate chains, lipids or phosphates

  -modifying amino acids and formation of bonds e.g. disulfide bridges

  -folding or shortening of proteins

  -modification by cAMP
• cAMP in glucagon signalling


  -glucagon binds to a receptor on plasma membrane of target cell-activates a transmembrane protein which activates G protein

  -this activates adenyl cyclase

  -this catalyses formation of cAMP from ATP

  -cAMP activates protein kinases(PKA)

  -PKA catalyses phosphorylation of various proteins hydrolysing ATP in the process

  -1 of these proteins could be a transcription factor and enter the nucleus and regulate transcription
• Homeobox sequence


  section of DNA 180 base pairs long coding for a part of the protein 60 amino acids long that is highly conserved in plants, animals and fungi.