7.1.1 DNA Structure

• Unlike most prokaryotic DNA which is referred to as ‘naked’, eukaryotic nuclear DNA is associated with proteins called histones (to form chromatin)
• Histones package the DNA into structures called nucleosomes
  • The nucleosome consists of a strand of DNA coiled around a core of eight histone proteins (octamer) to form a bead-like structure
  • DNA takes two turns around the histone core and is held in place by an additional histone protein
  • The DNA molecule continues to be wound around a series of nucleosomes to form what looks like a ‘string of beads’
• Nucleosomes help to supercoil the DNA, resulting in a compact structure which saves space within the nucleus
  • Nucleosomes also help to protect DNA and facilitate movement of chromosomes during cell division
  • An analogy for supercoiling is twisting an elastic band repeatedly until it forms additional coils
• Nucleosomes can be tagged with proteins to promote or suppress transcription

NOS Making careful observations—Rosalind Franklin’s X-ray diffraction provided crucial evidence that DNA is a double helix. 

• In the 1950s Rosalind Franklin and Maurice Wilkins used a technique called X-ray diffraction to study the structure of DNA
  • Franklin’s work was instrumental to Crick and Watson's model as the diffraction patterns indicated that DNA had a double-helical structure
• X-ray diffraction involves directing a beam of X-rays onto the molecule being studied
  • X-rays have a shorter wavelength and higher energy than visible light
• The short wavelength allows X-rays to pass through the molecule, interacting with any electrons within the atoms
  • The interaction causes X-rays to scatter (diffraction) at angles that indicate the arrangement of atoms
  • The scattering pattern can be recorded on a film (similar to having an X-ray of a bone), with dark marks appearing where the X-rays strike the film
  • Rotating the sample allows for the three-dimensional molecular structure to be studied
• Franklin was able to refine her methods and produce a clear diffraction pattern of DNA
• Using mathematical techniques and available knowledge about DNA, Franklin deduced that
  • DNA strands were helices - as represented by the X-shape
  • The pitch of the helix - as represented by the angle of the X-shape
  • The distance between nucleotides
  • Phosphates are located on the outside of the molecule
  • DNA was double stranded

• The discovery of the structure of DNA was due to experimental evidence and inputs from a range of independent researchers
  • Franklin’s X-ray diffraction patterns identified a compact double helix
  • Erwin Chargaff showed that DNA was composed of an equal number of purine and pyrimidine bases which suggested base pairing
  • Crick and Watson used this evidence to build various physical models of DNA
  • One model had the bases facing outwards but Franklin argued they should face inwards due to their hydrophobic nature
  • It was determined that if adenine paired with thymine and cytosine paired with guanine in an antiparallel orientation a highly compact structure would result
• When Crick and Watson proposed their model for the structure of DNA, they realised that the double stranded structure suggested a mechanism for its replication during the cell cycle
  • This was a key question that any model would have to address
• Crick and Watson stated that as one chain of the double helix was the complement of the other, either chain could act as a template during replication
  • They postulated that hydrogen bonds break, allowing separation of the chains
  • Each separate chain then acts as a template for the formation of a new complementary chain on itself
• This theory was called semi-conservative DNA replication as half of the original DNA molecule is kept (conserved) in each of the two new DNA molecules
• An opposing theory suggested DNA replicated ‘conservatively’
  • The entire original DNA double helix would stay together and serve as a template for a new DNA molecule
• Crick and Watsons' theory of semi-conservative DNA replication was later proven by Meselson and Stahl