• 1953:

 James  Watson  and  Francis  Crick  create  double  helical  model  for  DNA  
• After  Morgan  showed  genes  are  located  on  chromosomes,  it  sparked  the  debate  of  
DNA  and  protein  being  the  candidates  for  the  genetic  material  
• Much  was  known  about  proteins  
o Had  great  heterogeneity  and  specificity  of  function  
 Essential  for  the  hereditary  material  
• Little  was  known  about  nucleic  acids  
o Their  chemical  and  physical  properties  seemed  to  uniform  to  account  for  the  
multitude  of  inherited  traits  
• Frederick  Griffith:  1928  British  Medical  Officer  
o Studied  streptococcus  pneumoniae-­‐  pneumonia  causing  bacteria  
o Had  two  strains-­‐  a  pathogenic  and  a  harmless  
o When  he  killed  the  pathogenic  strain  with  heat  and  mixed  with  the  harmless  
strain  ,  some  cells  transformed  into  pathogenic  cells  
 Transformation:  a  change  in  genotype  and  phenotype  due  to  
assimilation  of  external  DNA  by  a  cell  
• Oswald  Avery:  1944  American  Bacteriologist  
o Built  on  Griffith’s  work  and  proved  that  DNA  was  the  responsible  agent  for  
transformation  
o Colleagues:  Maclyn  McCarty  and  Colin  MacLeod  
o Experiment:  Separate  each  part  of  the  bacteria  and  test  one  by  one  
o Skepticism  arose  because  not  much  was  known  about  DNA  
• Viruses  provided  additional  evidence  for  DNA  as  the  genetic  material  
o To  reproduce,  viruses  must  infect  and  take  over  a  cell’s  metabolic  machinery  
o Bacteriophages  (phages):  Viruses  that  infect  bacteria  
• 1952:  Alfred  Hershey  and  Martha  Chase  
o Showed  that  DNA  was  the  genetic  material  of  a  phage  was  known  as  T2  
 T2  was  all  DNA  and  a  little  protein  
 Proved  that  DNA  was  the  genetic  material  by  growing  T2  with  E.  Coli  
• Two  sets  of  petri  dishes  were  prepped-­‐  one  with  Sulfure-­‐35  to  
stain  the  protein  and  one  with  Phosphorous-­‐32  to  stain  DNA  
 • After  letting  the  T2  and  E.  Coli  mingle,  they  noticed  that  the  
inside  of  the  E.  Coli  cells  were  blue-­‐  showing  that  DNA  entered  
the  cell  
• Erwin  Chargraff:  Biochemist  
o Analyzed  the  base  composition  of  the  DNA  from  multiple  euakryotes  
 Noticed  that  all  the  four  bases  (A,  C,  T,  G)  were  present  in  eukaryotes,  
but  in  characteristic  ratios  that  varied  from  eukaryote  to  eukaryote  
 Chargraff’s  Rule:  The  amount  of  Adenine  approximately  equaled  the  
amount  of  Thymine  and  the  amount  of  Guanine  approximately  
equaled  the  amount  of  Cytosine  
• Once  biologists  accepted  DNA  as  the  genetic  material,  they  needed  to  know  it’s  
structure  
o Watson  and  Crick  used  X-­‐ray  crystallography  pictures  from  Rosalind  
Franklin  
o Watson  was  familiar  with  the  types  of  patterns  that  helical  molecules  
produce  in  X-­‐  ray  crystallographies  
 The  picture  told  Watson  that  the  structure  was  helical  and  enabled  
him  to  deduce  the  width  of  the  helix  and  the  spacing  of  the  
nitrogenous  bases  along  it  
• The  width  showed  that  the  helix  was  two  stranded  
o The  crystallography  showed  that  the  helix  makes  one  full  turn  every  3.4  
nanometer  (nm)  
 Bases  are  stacked  0.34  nm  apart  
• 10  layers  of  base  pairs  in  each  turn  on  the  helix  
o Adenine  pairs  with  Thymine  
o Guanine  pairs  with  Cytosine  
 Purine  +  Purine=  too  wide  
 Pyrimadine  +  Pyrimadine=  too  narrow  
 Purine  +  Pyrimadine=  width  consistent  with  X-­‐ray  data  
• The  Watson-­‐  Crick  model  proved  Chargraff’s  rule  
 • When  a  cell  copies  a  DNA  molecule,  each  strand  serves  as  a  blueprint,  demanding  
certain  nucleotides  to  make  a  complementary  strand.  
o Semiconservative  Model:  Type  of  DNA  replication  in  which  the  replicated  
double  helix  consists  of  one  old  strand,  derived  from  the  old  molecule,  and  
one  newly  made  strand  
• Humans  have  about  6  billion  base  pairs  per  cell  
o Only  takes  a  few  hours  to  copy  all  this  DNA  
o Only  a  few  errors  per  1  billion  nucleotides  
• More  than  a  dozen  enzymes  and  proteins  participate  in  DNA  replication  
• DNA  replication  starts  at  special  sites  
o Origins  of  replication:  special  sites  on  DNA  where  replication  starts  
o Proteins  attach  to  DNA  and  begin  to  unzip  the  DNA  into  two  strands  
o Replication  occurs  from  both  top  to  bottom  and  bottom  to  top  
simultaneously  
o DNA  Polymerases:  enzymes  that  catalyze  the  replication  of  DNA  strands  
o Rate  of  replication  is  500  million  nucleotides  per  second  
 Human  replication  occurs  at  50  million  nuecleotides  per  second  
o Nucleoside  triphosphates  serve  as  substrates  for  DNA  Polymerase  
• The  two  DNA  sugar-­‐  phosphate  backbones  run  anti-­‐parallel  to  eachother  (parallel  
but  in  opposite  directions)  
 
 
 
Picture  showing   the  antiparallel  
structure  of  the   DNA  Double  Helix  
Structure  
The  numbers  3   and  5  refer  to  the  
carbons  in  the  the   backbone.    
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Leading  Strand:  The  new  continuous  complementary  DNA  strand  synthesized  
along  the  template  strand  in  the  mandatory  5’3’  direction  
• Lagging  Strand:    A  discontinuously  synthesized  DNA  strand  that  elongates  in  a  
direction  away  from  the  replication  fork  
o First  synthesized  as  a  series  of  pigments-­‐  known  as  Okazaki  fragments  
o Pigments  are  about  100-­‐200  nucleotides  in  length  
 • DNA  ligase  joins  the  sugar-­‐phosphate  backbones  of  the  Okazaki  Fragments  to  create  
a  single  DNA  strand  
• Replication  of  cellular  DNA:  

 
• Helicase  is  an  enzyme  that  untwists  the  double  helix  at  the  replication  fork.    
 
Summary  of  DNA  Replication: