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What goes wrong with DNA?

What goes wrong with DNA?

  • A mistake in translation can produce mRNA with one or more incorrect codons
  • Error in cystic fibrosis sufferers is in the DNA as the problems are in every epithelial cell
  • Mistakes arise when DNA copies itself curing the process of DNA replication

 

DNA replication:

  • When a cell divides an exact copy of the DNA must be produced so that each daughter cell receives a copy – replication
  • DNA double helix unwinds from one end, the two strands split apart as the hydrogen bonds between bases break
  • Free DNA nucleotides line up alongside each DNA strand and hydrogen bonds form between the complimentary bases
  • The enzyme DNA polymerase links the adjacent nucleotides to form a complimentary strand
  • Each strand of DNA acts as a template on which a new strand is built; two complete DNA molecules are formed
  • Each of the two new DNA molecules contains one old strand and one new strand – semi-conservative replication

 

 

Semi-conservative replication:

  • Meselson and Stahl did experiments to show how DNA replicated
  • Three possible ways to replicate; fragmentary, conservative, semi-conservative

 

  • Uses light and heavy strands of DNA; achieved by using bacteria that had been grown in a medium containing only the heavy isotope nitrogen, 15
  • All the nucleotides in bacteria started out with heavy nitrogen, making the DNA denser than usual (yellow strand)
  • Then moved bacteria to a medium containing only normal 14N, meaning all new nucleotides introduced into the replicated DNA were light
  • Original; heavy / new; light
  • Bacteria was allowed to divide and replicated before being extracted and centrifuged
  • When centrifuged the heavy DNA sinks to the bottom while light DNA collects near the top, medium in the middle
  • The result: one medium band density (no heavy density left – excluding the conservative model)
  • After the DNA was extracted and centrifuged after two rounds of replication gave two bands (one medium, and one light)
  • Confirmed semi-conservative model and ruled out fragmentary (that would only be light and heavy)

 

Mistakes in replication:

  • As the new strand is being built an incorrect base may slip into place – mutation
  • Sometimes mutations occur in the DNA of an ovary or testis cell that is dividing to form an egg or sperm. This may be passed onto future generations
  • Some mutations have no effect
  • Genetic disorder; mutation within the gene, and a new base triplet is created that codes for a stop or different amino acid

 

Sickle Cell Anaemia:

  • Mutation in the gene that codes for one of the polypeptide chains in haemoglobin (the pigment in red blood cells which carries oxygen around the body)
  • Adenine replaces thymine along the chain
  • Protein produced contains the non-polar amino acid valine rather than polar glutamic acid
  • Haemoglobin made less soluble
  • Distorted shape; oxygen levels are low, molecules form long fibres that stick together inside the cell
  • The sickle shaped cells carry less oxygen and can block blood vessels

 

Mutations and Cystic Fibrosis:

  • Hundreds of mutations; affect the CFTR protein in different ways
  • Sometimes ATP is unable to bind and open the ion channel
  • In other cases the channel is open but changes in the protein structure lead to reduced movement in chloride ions through the channel
  • Most common mutation; deletion of three nucleotides (loss of phenylalanine – causing misfolding of protein)