DNA and the Molecular Basis of Heredity


The Search for the Basis of Heredity

T.H. Morgan Frederick Griffith, 1928 Oswarld Avery, Maclyn McCarty, and Colin MacLeod (1944) Alfred Hershey and Martha Chase (1952)
Additional Evidence That DNA Is the Genetic Material of Cells James Watson and Francis Crick - The Double Helix Model of DNA

There was a race to elucidate the 3-D structure of DNA

The Watson-Crick Model of DNA
 

Structure of Deoxyribose

 


DNA Replication - is DNA replication conservative, semiconservative, or dispersive?

 
Conservative - old strand acts as a template
  • One daughter strand is the original template while the other strand is composed entirely out of new nucleotides 
Dispersive Model
  • Each strand of both daughter molecules contains a mixture of old and newly synthesized DNA parts
Semiconservative - old strand splits apart and acts as a template 
  • Both daughter strands are composed of one of the old strands and one comprised out of new nucleotides
Isotopes were used to prove that DNA replication was semiconservative 
  • How was this done? 

The Meselson - Stahl Experiment


DNA Replication

It is very important to know that DNA replication is not a passive and spontaneous process. Many enzymes are required to unwind the double helix and to synthesize a new strand of DNA. We will approach the study of the molecular mechanism of DNA replication from the point of view of the machinery that is required to accomplish it. The unwound helix, with each strand being synthesized into a new double helix, is called the replication fork.

The Enzymes of DNA Replication

The Steps of DNA Replication
 
  • A portion of the double helix is unwound by a helicase. 
  • A molecule of DNA polymerase binds to one strand of the DNA and begins moving along it in the 3' to 5' direction, using it as a template for assembling a leading strand of nucleotides and reforming a double helix. 
  • Because DNA synthesis can only occur 5' to 3', a second DNA polymerase molecule is used to bind to the other template strand as the double helix opens. This molecule must synthesize discontinuous segments of polynucleotides (called Okazaki fragments). Another enzyme, DNA ligase then stitches these together into the lagging strand

Speed of Replication
 


Click here to see a shockwave graphic on DNA replication

Enzymes Proofread DNA During Its Replication and Repair Damage in Existing DNA

We cannot attribute the accurate of DNA replication solely to the specificity of base pairing



Telomeres - The DNA Synthesis Termination Paradox

For linear DNA (i.e. eukaryotic chromosomes) the fact that DNA polymerase can only add nucleotides to the 3' end of a preexisting polynucleotide presents a serious problem